Obstructive Sleep Apnea Treatment Devices, Systems and Methods

ABSTRACT

Devices, systems and methods for nerve stimulation for OSA therapy.

RELATED APPLICATIONS

The present case claims the benefit of U.S. Provisional PatentApplication No. 60/851,386 filed Oct. 13, 2006 and U.S. ProvisionalPatent Application No. 60/918,257 filed Mar. 14, 2007, both titledOBSTRUCTIVE SLEEP APNEA TREATMENT DEVICES, SYSTEMS AND METHODS, theentire disclosures of which are fully incorporated herein by reference.

FIELD OF THE INVENTION

The inventions described herein relate to devices, systems andassociated methods for treating sleeping disorders. More particularly,the inventions described herein relate to devices, systems and methodsfor treating obstructive sleep apnea.

BACKGROUND OF THE INVENTION

Obstructive sleep apnea (OSA) is highly prevalent, affecting one in fiveadults in the United States. One in fifteen adults has moderate tosevere OSA requiring treatment. Untreated OSA results in reduced qualityof life measures and increased risk of disease including hypertension,stroke, heart disease, etc.

Continuous positive airway pressure (CPAP) is a standard treatment forOSA. While CPAP is non-invasive and highly effective, it is not welltolerated by patients. Patient compliance for CPAP is often reported tobe between 40% and 60%.

Surgical treatment options for OSA are available too. However, they tendto be highly invasive (result in structural changes), irreversible, andhave poor and/or inconsistent efficacy. Even the more effective surgicalprocedures are undesirable because they usually require multipleinvasive and irreversible operations, they may alter a patient'sappearance (e.g., maxillo-mandibulary advancement), and/or they may besocially stigmatic (e.g., tracheostomy).

U.S. Pat. No. 4,830,008 to Meer proposes hypoglossal nerve stimulationas an alternative treatment for OSA. An example of an implantedhypoglossal nerve stimulator for OSA treatment is the Inspire™technology developed by Medtronic, Inc. (Fridely, Minn.). The Inspiredevice is not FDA approved and is not for commercial sale. The Inspiredevice includes an implanted neurostimulator, an implanted nerve cuffelectrode connected to the neurostimulator by a lead, and an implantedintra-thoracic pressure sensor for respiratory feedback and stimulustrigger. The Inspire device was shown to be efficacious (approximately75% response rate as defined by a 50% or more reduction in RDI and apost RDI of ≦20) in an eight patient human clinical study, the resultsof which were published by Schwartz et al. and Eisele et al. However,both authors reported that only three of eight patients remained freefrom device malfunction, thus demonstrating the need for improvements.

SUMMARY OF THE INVENTION

To address this and other unmet needs, the present invention provides,in exemplary non-limiting embodiments, devices, systems and methods fornerve stimulation for OSA therapy as described in the following detaileddescription.

BRIEF DESCRIPTION OF THE DRAWINGS

It is to be understood that both the foregoing summary and the followingdetailed description are exemplary. Together with the following detaileddescription, the drawings illustrate exemplary embodiments and serve toexplain certain principles. In the drawings:

FIG. 1 is a schematic diagram showing a fully implanted neurostimulatorsystem with associated physician programmer and patient controller fortreating obstructive sleep apnea;

FIG. 2 is a schematic diagram showing the implantable components of FIG.1 implanted in a patient;

FIG. 3 is a perspective view of the implantable components shown in FIG.1;

FIG. 4 is a detailed perspective view of the implantable neurostimulator(INS) shown in FIG. 3;

FIG. 5 is a detailed perspective view of the nerve cuff electrode andlead body shown in FIG. 3;

FIG. 6 is a close-up detailed perspective view of the nerve cuffelectrode shown in FIG. 3;

FIG. 7 is a detailed perspective view of the internal components of thenerve cuff electrode shown in FIG. 6;

FIG. 8 shows side and end views of an electrode contact of the nervecuff electrode shown in FIG. 7;

FIGS. 9A and 9B are perspective views of the respiration sensing leadshown in FIG. 3;

FIG. 10 schematically illustrates surgical access and tunneling sitesfor implanting the system illustrated in FIG. 2;

FIGS. 11A and 11B schematically illustrate dissection to a hypoglossalnerve;

FIG. 12 schematically illustrates various possible nerve stimulationsites for activating muscles controlling the upper airway;

FIGS. 13-22 are schematic illustrations of various stimulation lead bodyand electrode designs for use in a neurostimulator system;

FIGS. 23-24 schematically illustrate alternative implant procedures andassociated tools for the stimulation lead;

FIG. 25 schematically illustrates an alternative bifurcated lead bodydesign;

FIGS. 26A-26B schematically illustrate alternative fixation techniquesfor the stimulation lead and electrode cuff;

FIGS. 27A-27G schematically illustrate field steering embodiments;

FIGS. 28-33 schematically illustrate alternative fixation techniques forthe respiration sensing lead;

FIGS. 35A-35E and 36 schematically illustrate alternative electrodearrangements on the respiration sensing lead;

FIGS. 37 and 38A-38C schematically illustrate various anatomicalpositions or bio-Z vectors for the electrodes on the respiration sensinglead;

FIGS. 39-46 schematically illustrate alternative respiration signalprocessing techniques;

FIG. 47 schematically illustrates an alternative respiration detectiontechnique;

FIGS. 48-50 schematically illustrate alternative stimulation triggeralgorithms;

FIGS. 51A-51M are schematic illustrations of various external (partiallyimplanted) neurostimulation systems for treating obstructive sleepapnea;

FIGS. 52A-52G are schematic illustrations of a specific embodiment of anexternal (partially implanted) neurostimulation system;

FIGS. 53-56 schematically illustrate alternative screening tools; and

FIGS. 57A-57C schematically illustrate alternative intra-operativetools.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

The following detailed description should be read with reference to thedrawings in which similar elements in different drawings are numberedthe same. The drawings, which are not necessarily to scale, depictillustrative embodiments and are not intended to limit the scope of theinvention.

Description of Fully Implanted Neurostimulator System

With reference to FIG. 1, a neurostimulator system 10 includingimplanted components 20, physician programmer 30 and patient controller40 is shown schematically. The implanted components of the system 10 maygenerally include an implanted neurostimulator (INS) 50 (a.k.a.,implanted pulse generator (IPG)), an implanted stimulation lead (orleads) 60, and an implanted respiration sensing lead (or leads) 70. TheINS 50 generally includes a header 52 for connection of the leads 60/70,and a hermetically sealed housing 54 for the associated electronics andlong-life or rechargeable battery (not visible). The stimulation lead 60generally includes a lead body 62 with a proximal connector and a distalnerve electrode cuff 64. The respiration sensing lead 70 generallyincludes a lead body 72 with a proximal connector and one or moresensors 74 disposed on or along a distal portion thereof. Suitabledesigns of the INS 50, stimulation lead 60 and respiration sensing lead70 are described in more detail hereinafter.

As shown in FIG. 2, and by way of example, not limitation, the implantedcomponents 20 (shown faded) of the neurostimulator system 10 areimplanted in a patient P with the INS 50 disposed in a subcutaneouspocket, the stimulation lead body 62 disposed in a subcutaneous tunnel,the nerve cuff electrode 64 disposed on a nerve (e.g., hypoglossal nerve(HGN)) innervating a muscle (e.g., genioglossus muscle, not shown)controlling the upper airway, the respiration sensing lead body 72disposed in a subcutaneous tunnel, and the respiration sensors 74disposed adjacent lung tissue and/or intercostal muscles outside thepleural space.

Generally, electrical stimulus is delivered by the INS 50 via thestimulation lead 60 to a nerve innervating a muscle controlling upperairway patency to mitigate obstruction thereof. To reduce nerve andmuscle fatigue, the stimulus may be delivered for only a portion of therespiratory cycle, such as during inspiration which corresponds tonegative pressure in the upper airway. Stimulation may be thus triggeredas a function of respiration as detected by respiration sensing lead 70in a closed-loop feedback system. By way of example, the stimulus may betriggered to turn on at the end of expiration (or at the beginning ofinspiration), and triggered to turn off at the beginning of expiration(or at the end of inspiration). Triggering the stimulus as a function ofexpiration improves capture of the entire inspiratory phase, including abrief pre-inspiratory phase of about 300 milliseconds, thus more closelymimicking normal activation of upper airway dilator muscles.Over-stimulation may cause nerve and/or muscle fatigue, but a 40% to 50%duty cycle may be safely tolerated, thus enabling limitedover-stimulation. As an alternative, stimulus may be deliveredindependent of actual respiration wherein the stimulus duty cycle is setfor an average inspiratory duration at a frequency approximately equalto an average respiratory cycle.

Stimulus may be delivered to one or more of a variety of nerve sites toactivate one muscle or muscle groups controlling patency of the upperairway. For example, stimulation of the genioglossus muscle via thehypoglossal nerve moves or otherwise stiffens the anterior portion ofthe upper airway, thereby decreasing the critical pressure at which theupper airway collapses during inspiration and reducing the likelihood ofan apnea or hypopnea event occurring during sleep. Because the systemsdescribed herein work at the level of the tongue, it may be desirable tocombine this therapy with a therapy (e.g., UPPP or palatal implant) thatwork at the level of the soft palate, thus increasing efficacy for abroader range of patients.

With reference back to FIG. 1, the physician programmer 30 may comprisea computer 32 configured to control and program the INS 50 via awireless link to a programming wand 34. The physician programmer 30 maybe resident in a sleep lab where the patient undergoes apolysomnographic (PSG) study during which the patient sleeps while theINS 50 is programmed to optimize therapy.

The patient controller 40 may comprise control circuitry and associateduser interface to allow the patient to control the system via a wirelesslink while at home, for example. The patient controller 40 may include apower switch 42 to turn the system on and slowly ramp up when thepatient goes to sleep at night, and turn it off when the patient wakesin the morning. A snooze switch 44 may be used to temporarily put theINS 50 in standby mode for a preprogrammed period of time to allow thepatient to temporarily wake, after which the INS 50 turns back on andramps up to the desired stimulus level. A display 46 may be provided toindicate the status of the INS 50 (e.g., on, off or standby), toindicate satisfactory wireless link to the INS 50, to indicate remainingbattery life of the INS 50, etc. The patient controller may also haveprogrammability to adjust stimulus parameters (e.g., amplitude) withinpre-set range determined by the physician in order to improve efficacyand/or to reduce sensory perception, for example. Optionally, thepatient controller 40 may be configured to function as the programmingwand 34 of the physician programmer 30.

With reference to FIG. 3, the implanted components 20 are shownschematically with more detail. The implanted components include INS 50,stimulation lead 60, and respiration sensing lead 70. The INS 50includes header 52 and housing 54. The stimulation lead 60 includes leadbody 62 and nerve cuff electrode 64. The respiration sensing lead 70includes lead body 72 and respiration sensors 74 (e.g., impedancesensing electrodes).

With reference to FIG. 4, the INS 50 is shown schematically in moredetail. The INS 50 includes header 52 that may be formed usingconventional molding or casting techniques and may comprise conventionalmaterials such as epoxy or polyurethane (e.g., Tecothane brandpolyurethane). The housing 54 may be formed using conventional stampingor forming techniques and may comprise conventional materials such astitanium or ceramic. The housing 54 may include one or more isolatedelectrodes, and/or if a conductive material is used for the housing 54,the housing 54 may comprise an electrode, which may be used forrespiratory sensing, for example. The housing 54 may be hermeticallysealed to the header 52 using conventional techniques. The header 52 mayinclude two or more receptacles for receiving the proximal connectors66/76 of the stimulation lead body 62 and respiration sensing lead body72. The connectors 66/76 may comprise a conventional design such as IS1or other in-line designs. The header 52 may also include set screw sealsand blocks 56 for receiving set screws (not shown) that establishelectrical contact between the INS 50 and the conductors of the leads60/70 via connectors 66/76, and that establish mechanical fixationthereto. Some electrical contact may be achieved through spring type orcam-locked mechanisms. As shown, two set screw arrangements 56 are shownfor the stimulation lead 60 and four set screw arrangements 56 are shownfor the respiration sensing lead 70, but the number may be adjusted forthe number of conductors in each lead. A hole 58 may be provided in theheader 52 for securing the INS 50 to subcutaneous tissue using a sutureat the time of implantation.

The INS 50 may comprise a conventional implanted neurostimulator designused in neurostimulation applications, such as those available fromTexcel (US), CCC (Uruguay) and NeuroTECH (Belgium), but modified for thepresent clinical application in terms of stimulation signal parameters,respiratory signal processing, trigger algorithm, patient control,physician programming, etc. The INS may contain a microprocessor andmemory for storing and processing data and algorithms. Algorithms may bein the form of software and/or firmware, for example. One of severaldifferent embodiments of the neurostimulator may be implemented. Forexample, the neurostimulator may be an internal/implantedneurostimulator (INS) powered by a long-life primary battery orrechargeable battery, or an external neurostimulator (ENS) wirelesslylinked (e.g., inductive) to an implanted receiver unit connected to theleads. The INS (or the receiver unit of the ENS) may be implanted andoptionally anchored in a number of different locations including asubcutaneous pocket in the pectoral region, the dorsal neck region, orcranial region behind the ear, for example.

The INS 50 may include a long-life battery (not shown) which requiresperiodic replacement after years of service. Alternatively, the INS mayinclude a rechargeable power source such as a rechargeable battery orsuper capacitor that is used instead of the long-life battery. Tofacilitate recharging, the INS may include a receiver coil inductivelylinked to a transmitter coil that is connected to a recharging unitpowered by a larger battery or line power. Because the patient isstationary while sleeping, recharging may be scheduled to occur sometimeduring sleep to eliminate the need to carry the recharging unit duringdaily activities. The transmitter coil and the receiver coil may bearranged coaxially in parallel planes to maximize energy transferefficiency, and may be held in proximity to each other by a patch,garment, or other means as described with reference to the externalneurostimulator embodiments. Other examples of neurostimulator designswill be described in more detail hereinafter.

With reference to FIG. 5, the stimulation lead 60 may comprise a varietyof different design embodiments and may be positioned at differentanatomical sites. For example, a nerve cuff electrode(s) 64 may beattached to a nerve(s) innervating musculature affecting patency of theupper airway. As an alternative or in addition, the nerve cuff electrode64 may be replaced with an intramuscular electrode and placed directlyin the musculature affecting patency of the upper airway. The nerveelectrode 64 may be attached to a specific branch of a nerve innervatingthe desired muscle(s), or may be attached to a proximal trunk of thenerve in which a specific fascicle innervating the desired muscle(s) istargeted by steering the stimulus with multiple electrodes. One or moreelectrodes may be used for attachment to one or more portions of nerveson one side (unilateral) of the body, or one or more electrodes may beused for attachment to one or more portions of nerves on both sides(bilateral) of the body. Variations in lead body 62 and electrode 64design as well as variations in the target stimulation site or siteswill be described in more detail hereinafter.

With continued reference to FIG. 5, the lead body 62 may be sigmoidshaped, for example, to reduce strain applied to the cuff electrode 64when the lead body 62 is subject to movement. The sigmoid shape, whichmay alternatively comprise a variety of other waveform shapes, may havea wavelength of approximately 1.0 to 1.5 cm, and an amplitude ofapproximately 0.75 to 13 cm, for example. The lead body 62 may comprisea tubular jacket with electrical conductors 68 extending therein. Thetubular jacket may comprise extruded silicone having an outside diameterof approximately 0.047 inches and an inside diameter of approximately0.023 inches, for example. The tubular jacket may optionally have acovering of co-extruded polyurethane, for example, to improvedurability. The conductors 68, shown in a transparent window in thejacket for purposes of illustration only, may comprise a bifilar coil ofinsulated (e.g., ETFE) braided stranded wire (BSW) of MP35NLT material.The number of conductors 68 is shown as two, but may be adjusteddepending on the desired number of independent electrodes used.

With reference to FIG. 6, the nerve cuff electrode 64 may comprise acuff body 80 having a lateral (or superficial) side 82 and a medial (orcontralateral, or deep) side 84. The medial side 84 is narrower orshorter in length than the lateral side 82 to facilitate insertion ofthe medial side 84 around a nerve such that the medial side is on thedeep side of the nerve and the lateral side is on the superficial sideof the nerve. This configuration reduces the dissection of nervebranches and vascular supply required to get the cuff around a nerve.For the nerve cuff implant sites discussed herein, the medial side 84may have a length of less than 6 mm, and preferably in the range ofapproximately 3 to 5 mm, for example. The lateral side 82 may have alength of more than 6 mm, and preferably in the range of approximately 7to 8 mm, for example. The cuff body 80 may be compliant and may beavailable in different sizes with an inside diameter of approximately2.5 to 3.0 mm or 3.0 to 3.5 mm, for example. The cuff size may also beadjusted depending on the nominal diameter of the nerve at the site ofimplantation. The cuff body 80 may have a wall thickness ofapproximately 10 mm and may be formed of molded silicone, for example,and may be reinforced with imbedded fibers or fabrics. An integral towstrap 86 may be used to facilitate wrapping the cuff around a nerve byfirst inserting the strap 86 under and around the deep side of the nerveand subsequently pulling the strap to bring the medial side 84 inposition on the deep side of the nerve and the lateral side 82 on thesuperficial side of the nerve.

With continued reference to FIG. 6, the nerve cuff electrode 64 includeselectrode contacts 90A, 90B, and 90C imbedded in the body 80 of thecuff, with their inside surface facing exposed to establish electricalcontact with a nerve disposed therein. A transverse guarded tri-polarelectrode arrangement is shown by way of example, not limitation,wherein electrode contacts 90A and 90B comprise anodes transverselyguarding electrode contact 90C which comprises a cathode.

With this arrangement, the anode electrodes 90A and 90B are connected toa common conductor 68A imbedded in the body 80, and the cathodeelectrode 90C is connected to an independent conductor 68B extendingfrom the lateral side 82 to the medial side 84 and imbedded in the body80. By using the conductors 68 to make connections within the body 80 ofthe cuff 64, fatigue stresses are imposed on the conductors rather thanthe electrode contacts 90A, 90B and 90C.

With additional reference to FIGS. 7 and 8, the electrode contacts 90A,90B and 90C may thus be semi-circular shaped having an arc length ofless than 180 degrees, and preferably an arc length of approximately 120degrees, for example. Each electrode 90 may have two reverse bends(e.g., hooked or curled) portions 92 to provide mechanical fixation tothe body 80 when imbedded therein. Each electrode 90 may also have twocrimp tabs 94 defining grooves thereunder for crimping to the conductors68 or for providing a pass-through. As shown in FIG. 7, conductor 68Apasses through the grooves under the lower crimp tabs 94 of electrodes90B and 90A, loops 98 around through the grooves under the upper crimptabs 94 of electrodes 90A and 90B, is crimped 96 by the upper tabs 94 ofelectrodes 90A and 90B to provide mechanical and electrical connection,is looped again back between the crimp tabs 94 on the outside of theelectrode contact 90, and is resistance spot welded 95 to provideredundancy in mechanical and electrical connection. Also as shown inFIG. 7, conductor 68B passes through the groove under the lower crimptab 94 of electrode 90C, loops around through the groove under the uppercrimp tab 94 of electrode 90C, and is crimped by the upper tab 94 ofelectrode 90C to provide mechanical and electrical connection. Thisarrangement avoids off-axis tensile loading at the crimp sites 96 whichmay otherwise fail due to stress concentration, and the looped portion98 provides additional strain relief. FIG. 8 provides example dimensions(inches) of an electrode contact 90 for a 2.5 mm inside diameter cuff,wherein the electrode is formed of 90/10 or 80/20 platinum iridium alloyformed by wire EDM, for example.

With reference to FIGS. 9A and 9B, a distal portion of the respirationsensing lead 70 and a distal detail of the sensing lead 70,respectively, are shown schematically. In the illustrated embodiment,the respiration sensing lead 70 and associated sensors 74 are implantedas shown in FIG. 2. However, the respiration sensor(s) may comprise avariety of different design embodiments, both implanted and external,and may be positioned at different anatomical sites. Generally, therespiratory sensor(s) may be internal/implanted or external, and may beconnected to the neurostimulator via a wired or wireless link. Therespiratory sensor(s) may detect respiration directly or a surrogatethereof. The respiratory sensor(s) may measure, for example, respiratoryairflow, respiratory effort (e.g., diaphragmatic or thoracic movement),intra-pleural pressure, lung impedance, respiratory drive, upper airwayEMG, changes in tissue impedance in and around the lung(s) including thelungs, diaphragm and/or liver, acoustic airflow or any of a number otherparameters indicative of respiration. Detailed examples of suitablerespiration sensing leads and sensors will be described in more detailhereinafter.

With continued reference to FIGS. 9A and 9B, the respiration sensinglead 70 includes a lead body 72 and a plurality of respiration sensors74A-74D comprising ring electrodes for sensing bio-impedance. The leadbody 72 of the respiration sensing lead 70 may include a jacket covercomprising an extruded silicone tube optionally including a polyurethanecover (80A durometer), or may comprise an extruded polyurethane tube(55D durometer). The ring electrodes 74A-74D may comprise 90/10 or 80/20platinum iridium alloy tubes having an outside diameter of 0.050 inchesand a length of 5 mm, and secured to the jacket cover by laser weldingand/or adhesive bonding, for example. The lead body 72 may include aplurality of conductors 78 as seen in the transparent window in thejacket cover, which is shown for purposes of illustration only. Theconductors 78 may comprise insulated and coiled BSW or solid wire(optionally DFT silver core wire) disposed in the tubular jacket, withone conductor provided for each ring electrode 74A-74D requiringindependent control. Generally, the impedance electrodes 74A-74D maycomprise current emitting electrodes and voltage sensing electrodes fordetecting respiration by changes in bio-impedance. The number, spacing,anatomical location and function of the impedance electrodes will bedescribed in more detail hereinafter.

Description of Implant Procedure

With reference to FIG. 10, surgical access sites are schematically shownfor implanting the internal neurostimulator components 20 shown inFIG. 1. The internal neurostimulator components 20 may be surgicallyimplanted in a patient on the right or left side. The right side may bepreferred because it leaves the left side available for implantation ofa pacemaker, defibrillator, etc., which are traditionally implanted onthe left side. The right side may also be preferred because it lendsitself to a clean respiratory signal less susceptible to cardiacartifact and also offers placement of respiratory sensors across theinterface between the lung, diaphragm and liver for better detection ofimpedance changes during respiration.

With continued reference to FIG. 10, the INS (not shown) may beimplanted in a subcutaneous pocket 102 in the pectoral region, forexample. The stimulation lead (not shown) may be implanted in asubcutaneous tunnel 104 along (e.g., over or under) the platysma musclein the neck region. The respiration sensing lead (not shown) may beimplanted in a subcutaneous tunnel 106 extending adjacent the ribcage toan area adjacent lung tissue and/or intercostal muscles outside thepleural space. The nerve cuff electrode (not shown) may be attached to anerve by surgical dissection at a surgical access site 110 proximate thetargeted stimulation site. In the illustrated example, the target nerveis the right hypoglossal nerve and the surgical access site is in thesubmandibular region.

With reference to FIGS. 11A and 11B, a surgical dissection 110 to thehypoglossal nerve is shown schematically. A unilateral dissection isshown, but a bilateral approach for bilateral stimulation may also beemployed. Conventional surgical dissection techniques may be employed.The branch of the hypoglossal nerve (usually a medial or distal branch)leading to the genioglossus muscle may be identified by stimulating thehypoglossal nerve at different locations and observing the tongue forprotrusion. Because elongation and/or flexion may be mistaken forprotrusion, it may be desirable to observe the upper airway using aflexible fiber optic scope (e.g., nasopharyngoscope) inserted into thepatient's nose, through the nasal passages, past the nasopharynx andvelopharynx to view of the oropharynx and hypopharynx and visuallyconfirm an increase in airway caliber by anterior displacement(protrusion) of the tongue base when the nerve branch is stimulated.

The implant procedure may be performed with the patient under generalanesthesia in a hospital setting on an out-patient basis. Alternatively,local anesthesia (at the surgical access sites and along thesubcutaneous tunnels) may be used together with a sedative in a surgicalcenter or physician office setting. As a further alternative, a facialnerve block may be employed. After a post-surgical healing period ofabout several weeks, the patient may return for a polysomnographic (PSG)test or sleep study at a sleep center for programming the system andtitrating the therapy. A trialing period may be employed prior to fullimplantation wherein the hypoglossal nerve or the genioglossus muscle isstimulated with fine wire electrodes in a sleep study and the efficacyof delivering stimulus to the hypoglossal nerve or directly to thegenioglossus muscle is observed and measured by reduction in apneahypopnea index, for example.

Other nerve target sites are described elsewhere herein and may beaccessed by similar surgical access techniques. As an alternative tosurgical dissection, less invasive approaches such as percutaneous orlaparoscopic access techniques may be utilized, making use of associatedtools such as tubular sheaths, trocars, etc.

Description of Alternative Stimulation Target Sites

With reference to FIG. 12, various possible nerve and/or direct musclestimulation sites are shown for stimulating muscles controlling patencyof the upper airway. In addition to the upper airway which generallyincludes the pharyngeal space, other nerves and dilator muscles of thenasal passage and nasopharyngeal space may be selectively targeted forstimulation. A general description of the muscles and nerves suitablefor stimulation follows, of which the pharyngeal nerves and muscles areshown in detail in FIG. 12.

Airway dilator muscles and associated nerves suitable for activationinclude are described in the following text and associated drawings. Thedilator naris muscle functions to widen the anterior nasal aperture(i.e., flares nostrils) and is innervated by the buccal branch of thefacial nerve (cranial nerve VII). The tensor veli palatine musclefunctions to stiffen the soft palate and is innervated by the medial (orinternal) pterygoid branch of the mandibular nerve. The genioglossusmuscle is an extrinsic pharyngeal muscle connecting the base of thetongue to the chin and functions to protrude the tongue. Thegenioglossus muscle is typically innervated by a distal or medial branch(or braches) of the right and left hypoglossal nerve. The geniohyoidmuscle connects the hyoid bone to the chin and the sternohyoid muscleattaches the hyoid bone to the sternum. The geniohyoid muscle functionsto pull the hyoid bone anterosuperiorly, the sternohyoid musclefunctions to pull hyoid bone inferiorly, and collectively (i.e.,co-activation) they function to pull the hyoid bone anteriorly. Thegeniohyoid muscle is innervated by the hypoglossal nerve, and thesternohyoid muscle is innervated by the ansa cervicalis nerve.

By way of example, a nerve electrode may be attached to a specificbranch of the hypoglossal nerve innervating the genioglossus muscle(tongue protruder), or may be attached to a more proximal portion (e.g.,trunk) of the hypoglossal nerve in which a specific fascicle innervatingthe genioglossus muscle is targeted by steering the stimulus using anelectrode array. Activating the genioglossus muscle causes the tongue toprotrude thus increasing the size of anterior aspect of the upper airwayor otherwise resisting collapse during inspiration.

As an alternative to activation of any or a combination of the airwaydilator muscles, co-activation of airway dilator and airway restrictoror retruder muscles may be used to stiffen the airway and maintainpatency. By way of example, a nerve electrode may be attached tospecific branches of the hypoglossal nerve innervating the genioglossusmuscle (tongue protruder), in addition to the hyoglossus andstyloglossus muscles (tongue retruders), or may be attached to a moreproximal portion (e.g., trunk) of the hypoglossal nerve in whichspecific fascicles innervating the genioglossus, hyoglossus andstyloglossus muscles are targeted by steering the stimulus using anelectrode array. Activating the hyoglossus and styloglossus musclescauses the tongue to retract, and when co-activated with thegenioglossus, causes the tongue to stiffen thus supporting the anterioraspect of the upper airway and resisting collapse during inspiration.Because the tongue retruder muscles may overbear the tongue protrudermuscle under equal co-activation, unbalanced co-activation may bedesired. Thus, a greater stimulus (e.g., longer stimulation period,larger stimulation amplitude, higher stimulation frequency, etc.) or anearlier initiated stimulus may be delivered to the portion(s) of thehypoglossal nerve innervating the genioglossus muscle than to theportion(s) of the hypoglossal nerve innervating the hyoglossus andstyloglossus muscles.

With continued reference to FIG. 12, examples of suitable nervestimulation sites include B; A+C; A+C+D; B+D; C+D; and E. Sites B and Emay benefit from selective activation by field steering using anelectrode array. As mentioned before, nerve electrodes may be placed atthese target nerve(s) and/or intramuscular electrodes may be placeddirectly in the muscle(s) innervated by the target nerve(s).

Site A is a distal or medial branch of the hypoglossal nerve proximal ofa branch innervating the genioglossus muscle and distal of a branchinnervating the geniohyoid muscle. Site B is a more proximal portion ofthe hypoglossal nerve proximal of the branches innervating thegenioglossus muscle and the geniohyoid muscle, and distal of thebranches innervating the hyoglossus muscle and the styloglossus muscle.Site C is a medial branch of the hypoglossal nerve proximal of a branchinnervating the geniohyoid muscle and distal of branches innervating thehyoglossus muscle and the styloglossus muscle. Site D is a branch of theansa cervicalis nerve distal of the nerve root and innervating thesternohyoid Site E is a very proximal portion (trunk) of the hypoglossalnerve proximal of the branches innervating the genioglossus, hyoglossusand styloglossus muscles.

Activating site B involves implanting an electrode on a hypoglossalnerve proximal of the branches innervating the genioglossus muscle andthe geniohyoid muscle, and distal of the branches innervating thehyoglossus muscle and the styloglossus muscle.

Co-activating sites A+C involves implanting a first electrode on ahypoglossal nerve proximal of a branch innervating the genioglossusmuscle and distal of a branch innervating the geniohyoid muscle, andimplanting a second electrode on the hypoglossal nerve proximal of abranch innervating the geniohyoid muscle and distal of branchesinnervating the hyoglossus muscle and the styloglossus muscle.

Co-activating sites A+C+D involves implanting a first electrode on ahypoglossal nerve proximal of a branch innervating the genioglossusmuscle and distal of a branch innervating the geniohyoid muscle;implanting a second electrode on the hypoglossal nerve proximal of abranch innervating the geniohyoid muscle and distal of branchesinnervating the hyoglossus muscle and the styloglossus muscle; andimplanting a third electrode on a branch of an ansa cervicalis nervedistal of the nerve root and innervating the sternohyoid.

Co-activating sites B+D involves implanting a first electrode on ahypoglossal nerve proximal of branches innervating the genioglossusmuscle and the geniohyoid muscle, and distal of branches innervating thehyoglossus muscle and the styloglossus muscle; and implanting a secondelectrode on a branch of an ansa cervicalis nerve distal of the nerveroot and innervating the sternohyoid.

Co-activating sites C+D involves implanting a first electrode on ahypoglossal nerve proximal of a branch innervating the geniohyoidmuscle, and distal of branches innervating the hyoglossus muscle and thestyloglossus muscle and implanting a second electrode on a branch of anansa cervicalis nerve distal of the nerve root and innervating thesternohyoid.

Activating site E involves implanting an electrode on a hypoglossalnerve proximal of the branches innervating the genioglossus, hyoglossusand styloglossus muscles; and selectively activating (e.g., by fieldsteering) the genioglossus muscle before or more than the hyoglossus andstyloglossus muscles.

Description of Alternative Nerve Electrodes

Any of the alternative nerve electrode designs described hereinafter maybe employed in the systems described herein, with modifications toposition, orientation, arrangement, integration, etc. made as dictatedby the particular embodiment employed. Examples of other nerve electrodedesigns are described in U.S. Pat. No. 5,531,778, to Maschino et al.,U.S. Pat. No. 4,979,511 to Terry, Jr., and U.S. Pat. No. 4,573,481 toBullara, the entire disclosures of which are incorporated herein byreference.

With reference to the following figures, various alternative electrodedesigns for use in the systems described above are schematicallyillustrated. In each of the embodiments, by way of example, notlimitation, the lead body and electrode cuff may comprise the same orsimilar materials formed in the same or similar manner as describedpreviously. For example, the lead body may comprise a polymeric jacketformed of silicone, polyurethane, or a co-extrusion thereof. The jacketmay contain insulated wire conductors made from BSW or solid wirecomprising MP35N, MP35N with Ag core, stainless steel or Tantalum, amongothers. The lead body may be sigmoid shaped to accommodate neck andmandibular movement. Also, a guarded cathode tri-polar electrodearrangement (e.g., anode-cathode-anode) may be used, with the electrodesmade of 90/10 or 80/20 PtIr alloy with silicone or polyurethane backing.

With specific reference to FIGS. 13A and 13B, a self-sizing andexpandable design is shown to accommodate nerve swelling and/orover-tightening. FIG. 13A shows a perspective view of a nerve electrodecuff 130 on a nerve such as a hypoglossal nerve, and FIG. 13B shows across-sectional view of the nerve cuff electrode 130 on the nerve. Inthis embodiment, the implantable nerve cuff electrode 130 comprises acomplaint sheet wrap 132 configured to be wrapped about a nerve andsecured thereto by connecting opposite portions of the sheet by sutures138, for example. The sheet 132 includes a plurality of radially andlongitudinally distributed fenestrations 134 to allow expansion of thesheet 132 to accommodate nerve swelling and/or over tightening.Electrode contacts 136 comprising a coil, foil strip, conductiveelastomer or individual solid conductors may be carried by the sheet 132with an exposed inside surface to establish electrical contact with thenerve.

With specific reference to FIGS. 14A-14C, another self-sizing andexpandable design is shown to accommodate nerve swelling and/orover-tightening. FIG. 14A shows a perspective view of a nerve electrodecuff 140 on a nerve such as a hypoglossal nerve, and FIG. 14B shows across-sectional view of the nerve cuff electrode 140 on the nerve. Inthis embodiment, the implantable nerve cuff electrode 140 comprises acomplaint sheet wrap 142 configured to be wrapped about a nerve andsecured thereto by connecting opposite portions of the sheet by sutures148A, or by a buckle 148B as shown in FIG. 14C, for example. Theopposite portions of the sheet 142 comprise one or more narrow strips144 integral with the sheet 142 to allow expansion and to accommodatenerve swelling and/or over tightening. Electrode contacts 146 comprisinga coil, foil strip, conductive elastomer or individual solid conductorsmay be carried by the sheet 142 with an exposed inside surface toestablish electrical contact with the nerve.

With specific reference to FIGS. 15A-15C, another self-sizing andexpandable design is shown to accommodate nerve swelling and/orover-tightening. FIG. 15A shows a perspective view of a nerve electrodecuff 150 on a nerve such as a hypoglossal nerve, and FIG. 15B shows across-sectional view of the nerve cuff electrode 150 on the nerve. Inthis embodiment, the implantable nerve cuff electrode 150 comprises acomplaint sheet wrap 152 configured to be wrapped about a nerve andsecured thereto by connecting opposite portions of the sheet 152 bysutures 158, for example. The opposite portions of the sheet 152 areoffset from the nerve and a thickened portion of the sheet 152 fills theoffset space. The offset distance reduces the amount of compressiveforce that the electrode cuff can exert on the nerve. To further reducethe pressure on the nerve, the sheet 152 includes a plurality ofradially distributed slits 154 extending partly through the thickness ofthe sheet 152 to allow expansion and to accommodate nerve swellingand/or over tightening.

With specific reference to FIGS. 16A and 16B, another self-sizing andexpandable design is shown to accommodate nerve swelling and/orover-tightening. FIG. 16A shows a perspective view of a nerve electrodecuff 160 on a nerve such as a hypoglossal nerve, and FIG. 16B shows across-sectional view of the nerve cuff electrode 160 on the nerve. Inthis embodiment, the implantable nerve cuff electrode 160 comprises acomplaint sheet wrap 162 configured to be wrapped about a nerve andsecured thereto by connecting opposite portions of the sheet 162 bysutures 168, for example. The sheet 162 includes a plurality of radiallydistributed and longitudinally extending convolutions 164 that maycomprise alternative thick 164A and thin 164B portions in the sheet 162and/or overlapping portions 164C of the sheet 162 to allow expansion andto accommodate nerve swelling and/or over tightening. Electrode contacts166 comprising a coil, foil strip, conductive elastomer or individualsolid conductors may be carried by the sheet 162 with an exposed insidesurface to establish electrical contact with the nerve. Nerve cuffelectrode 160 may accommodate one or two lead bodies 62A, 62B forconnection to the electrode contacts 166 on the same or opposite sidesof the nerve.

With reference to FIG. 17, a modular nerve electrode cuff 170 is shownthat includes a semi-cylindrical body portion 172 with an array ofelectrode contacts 176 with separate insulative strips 174 for placementon the deep (contralateral side) of the nerve, which typically has morenerve branches and connecting blood vessels. In this embodiment,independent placement of the electrode body 172 on the superficial(lateral) side of the nerve and placement of the insulative strips 174on the deep (contralateral) side of the nerve minimizes dissection. Thestrips 174 may be connected to the electrode body 172 by sutures orbuckles as described previously. This embodiment is also self-sizing toaccommodate nerve swelling and/or over-tightening.

With reference to FIG. 18, a nerve cuff electrode 180 is shown that hasa cuff body with a relatively wide semi-cylindrical lateral side 182 anda relatively narrow semi-cylindrical medial side 184 that may extendthrough a small fenestration around the deep (contralateral) side of anerve to securely and gently grasp the nerve while minimizingdissection. In the illustrated example, the lateral side 182 carries twoanode electrode contacts 186 and the medial side 184 carries one cathodeelectrode contact 186 in an arrangement that may be referred to astransverse guarded tri-polar. A tow strap 188 is provided for insertingthe medial side 184 around the deep side of the nerve. The tow strap 188may be integrally formed with the medial side 184 of the cuff body, andmay include a reinforced tip 188A with a serrated or marked cut line188B.

With reference to FIGS. 19A and 19B, a nerve cuff electrode 190 is shownthat has a cuff body with a relatively wide semi-cylindrical lateralside 192 and a relatively narrow semi-cylindrical medial side 194 thatmay extend through a small fenestration around the deep (contralateral)side of a nerve to securely and gently grasp the nerve while minimizingdissection. In the illustrated example, the lateral side 192 carries onecathode electrode contact 196C and two guarding anode electrode contacts196B and 196D, and the medial side 194 carries one anode electrodecontact 196A in an arrangement that may be referred to as transverse andlongitudinal guarded quad-polar. The provision of guarding electrodecontacts 196B and 196C reduces extrinsic stimulation due to the lack ofinsulative material on the medial side 194. The embodiments of FIGS. 18,19A and 19B illustrate two different electrode contact arrangements, butthe number and arrangement may be modified to suit the particularapplication.

With reference to FIG. 20, a nerve cuff electrode array 200 is shownthat utilizes a series of relatively narrow independent cuffs 200A, 200Band 200C with corresponding independent lead bodies 62. Providing aseries of relatively narrow independent cuffs 200A, 200B and 200Cminimizes the required dissection around the nerve for implantationthereof. Also, the series of independent cuffs 200A, 200B and 200Callows more selectivity in electrode placement to adjust for anatomicalvariation or multiple target stimulation sites, for example. Providingmultiple independent lead bodies 62 allows for more options in routingand placement of the individual lead bodies 62 (e.g., alternateplacement of lead body 62A) and also prevents tissue encapsulationaround the lead bodies 62 from collectively affecting encapsulation ofthe nerve cuffs 200. Each of the cuffs 200A, 200B and 200C may include acuff body 202 with one or more imbedded electrode contacts (not shown)and a tow strap 204 as described before. Also, each of the cuffs 200A,200B and 200C may include suture 208 or a buckle 206 to lock onto thetow strap 204 for connecting opposite ends of the body 202 around thenerve.

With reference to FIGS. 21A and 21B, a nerve cuff electrode 210 is shownwith multiple electrode contacts 216 radially spaced around the insidesurface of a compliant split cuff body 212 to establish multipleelectrical contact points around the circumference of the nerve. Each ofthe electrode contacts 216 may be connected to independent conductors inthe lead body 62 via axially extending wires 217. This arrangementallows for field steering as discussed herein. The compliant split cuffbody 212 together with axially extending wires 217 allows forself-sizing to accommodate nerve swelling and/or over-tightening. One ormore pairs of tabs 214 extending from opposite end portions of the cuffbody 212 may be connected by a suture (not shown) as described herein.As shown in FIG. 21B, the proximal and distal ends of the cuff body 212may have tapered thickness extensions 218 to provide strain relief andreduce mechanical irritation of the nerve due to contact with the edgeof the cuff.

With reference to FIG. 22, a nerve cuff electrode 220 is shown with aseparable lead 62 in what may be referred to as a modular design. Inthis embodiment, the nerve cuff electrode 220 includes a semi-circularflexible cuff body (or housing) 222 with a receptacle 224 configured toaccommodate a distal end of a lead body 62 therein. The receptacle 224may provide a releasable mechanical lock to the lead body 52 as by apress fit, mating detents, etc. The distal end of the lead body 62carries an array of ring electrodes 65, with windows 226 provided in thecuff body 222 configured to align with the ring electrodes 65 and permitexposure of the ring electrodes 65 to the nerve to establish electricalconnection therebetween. The cuff body 222 may be attached to the nerveor simply placed adjacent the nerve. Any of the cuff designs describedherein may be provided with a receptacle to accommodate a removable leadbody. This embodiment allows postoperative removal of the lead body 62without removal of the cuff 220, which may be beneficial in revisionoperations, for example.

Description of Alternative Implant Procedure for the Stimulation Lead

With reference to FIGS. 23A-23C, an insertable paddle-shaped lead 230design is shown. The insertable lead 230 may have a paddle-shape(rectangular) cross-section with a tubular jacket 232 and one or moreconductors 234 extending therethrough to one or more distally placedelectrode contact(s) 236. The electrode contacts) 236 may be imbedded ina molded distal end of the jacket 232 such that the electrode contact236 has an exposed surface to face the nerve when implanted as shown inFIG. 23B. The space between the nerve and electrode is shown forpurposes of illustration only, as the electrodes may be placed in directcontact with the nerve. Soft tines 238 may be integrally formed at thedistal end of the tubular jacket 232 for purposes of mild fixation totissue when implanted. The insertable lead 230 is configured to beplaced adjacent to the nerve (thereby negating the need for a cuff) byinserting the lead 230 at the surgical access site 110 and following thenerve distally until the electrode contacts 236 are placed adjacent thetarget stimulation site. The insertable lead 232 may be used alone or inconjunction with another lead as shown in FIGS. 23B and 23C. In theillustrated example, a first lead 230A is inserted along a superficialside of the nerve and a second lead 230B is inserted along a deep sideof the nerve.

A method of implanting lead 230 may generally comprise accessing aproximal extent of the nerve by minimal surgical dissection andretraction of the mylohyoid muscle as shown in FIG. 23C. Special toolsmay alternatively be employed for percutaneous or laparoscopic access asshown and described with reference to FIGS. 24A-24C. Subsequently, twopaddle-shaped leads 230 with distal electrode contacts 236 may beinserted into the surgical access site and advanced beyond the accesssite along a distal aspect of the nerve to the desired stimulation siteon either side of the nerve. These techniques minimize trauma andfacilitate rapid recovery.

A less invasive method of implanting a paddle-shaped lead 230 is shownin FIGS. 24A-24C. In this embodiment, a rectangular tubular trocar 240with a sharpened curved tip is placed through a percutaneous access site111 until a distal end thereof is adjacent the superficial side of thenerve. A paddle-shaped lead 230 is inserted through the lumen of thetrocar 240 and advanced distally beyond the distal end of the trocar 240along the nerve, until the electrode contacts 236 are positioned at thetarget stimulation site. As shown in FIG. 24B, which is a view takenalong line A-A in FIG. 24A, the insertable lead 230 includes multipleelectrode contacts 236 in an anode-cathode-anode arrangement, forexample, on one side thereof to face the nerve when implanted. In thisembodiment, tines are omitted to facilitate smooth passage of the lead230 through the trocar. To establish fixation around the nerve and toprovide electrical insulation, a backer strap 242 of insulative materialmay be placed around the deep side of the nerve. To facilitatepercutaneous insertion of the backer 242, a curved tip needle 244 may beinserted through a percutaneous access site until the tip is adjacentthe nerve near the target stimulation site. A guide wire 246 with aJ-shaped tip may then be inserted through the needle 244 and around thenerve. The backer 242 may then be towed around using the guide wire 246as a leader, and secured in place by a buckle (not shown), for example.

With reference to FIG. 25, a bifurcated lead 250 is shown to facilitateseparate attachment of electrode cuffs 64 to different branches of thesame nerve or different nerves for purposes described previously. Any ofthe nerve cuff electrode or intramuscular electrode designs describedherein may be used with the bifurcated lead 250 as shown. In theillustrated example, a first lead furcation 252 and a second leadfurcation 254 are shown merging into a common lead body 62. Eachfurcation 252 and 254 may be the same or similar construction as thelead body 62, with modification in the number of conductors. More thantwo electrode cuffs 64 may be utilized with corresponding number of leadfurcations.

Description of Stimulation Lead Anchoring Alternatives

With reference to FIGS. 26A and 26B, an elastic tether 264 with alimited length is utilized to prevent high levels of traction on theelectrode cuff 64 around the hypoglossal nerve (or other nerve in thearea) resulting from gross head movement. In other words, tether 264relieves stress applied to the electrode cuff 64 by the lead body 62.FIGS. 26A and 26B are detailed views of the area around the dissectionto the hypoglossal nerve, showing alternative embodiments of attachmentof the tether 264. The proximal end of the tether 264 may be attached tothe lead body 62 as shown in FIG. 26A or attached to the electrode cuff64 as shown in FIG. 26B. The distal end of the tether 264 may beattached to the fibrous loop carrying the digastrics tendon as shown inFIG. 26A or attached to adjacent musculature as shown in FIG. 26B.

By way of example, not limitation, and as shown in FIG. 26A, a tubularcollar 262 is disposed on the lead body 62 to provide connection of thetether 262 to the lead body 62 such that the lead body 62 is effectivelyattached via suture 266 and tether 264 to the fibrous loop surroundingthe digastrics tendon. The tether 264 allows movement of the attachmentpoint to the lead body 62 (i.e., at collar 262) until the tether 264 isstraight. At this point, any significant tensile load in the caudaldirection will be borne on the fibrous loop and not on the electrodecuff 64 or nerve. This is especially advantageous during healing beforea fibrous sheath has formed around the lead body 62 and electrode cuff64, thus ensuring that the cuff 64 will not be pulled off of the nerve.It should be noted that the length of the tether 262 may be less thanthe length of the lead body 62 between the attachment point (i.e., atcollar 262) and the cuff 64 when the tensile load builds significantlydue to elongation of this section of lead body 62.

The tether 264 may be formed from a sigmoid length of braided permanentsuture coated with an elastomer (such as silicone or polyurethane) tomaintain the sigmoid shape when in the unloaded state. The tether 264may also be made from a monofilament suture thermoformed or molded intoa sigmoid shape. The distal end of the tether 264 may be attached to thefibrous loop using a suture 266 or staple or other secure means. Notethat the tether 264 may be made from a biodegradable suture that willremain in place only during healing.

Also by way of example, not limitation, an alternative is shown in FIG.26B wherein the tether 264 is attached to the electrode cuff 64. Thedistal end of the tether 264 may be attached to the adjacent musculatureby suture 266 such the musculature innervated by branches of thehypoglossal nerve or other musculature in the area where the electrodecuff 64 is attached to the nerve. The tether 264 ensures that theelectrode cuff 64 and the hypoglossal nerve are free to move relative tothe adjacent musculature (e.g., hyoglossal). As significant tensile loadis applied to the lead body 62 due to gross head movement, the tether264 will straighten, transmitting load to the muscle rather then to thenerve or electrode cuff 64.

Description of Field Steering Alternatives

With reference to FIGS. 27A-27G, a field steering nerve cuff electrode64 is shown schematically. As seen in FIG. 27A, the nerve cuff electrode64 may include four electrode contacts 90A-90D to enable field steering,and various arrangements of the electrode contacts 90A-90D are shown inFIGS. 27B-27G. Each of FIGS. 27B-27G includes a top view of the cuff 64to schematically illustrate the electrical field (activating function)and an end view of the cuff 64 to schematically illustrate the area ofthe nerve effectively stimulated. With this approach, electrical fieldsteering may be used to stimulate a select area or fascicle(s) within anerve or nerve bundle to activate select muscle groups as describedherein.

With specific reference to FIG. 27A, the nerve cuff electrode 64 maycomprise a cuff body having a lateral (or superficial) side 82 and amedial (or contralateral, or deep) side 84.

The medial side 84 is narrower or shorter in length than the lateralside 82 to facilitate insertion of the medial side 84 around a nervesuch that the medial side is on the deep side of the nerve and thelateral side is on the superficial side of the nerve. An integral towstrap 86 may be used to facilitate wrapping the cuff around a nerve. Thenerve cuff electrode 64 includes electrode contacts 90A, 90B, 90C and90D imbedded in the body of the cuff, with their inside surface facingexposed to establish electrical contact with a nerve disposed therein.Electrode contacts 90A and 90B are longitudinally and radially spacedfrom each other. Electrode contacts 90C and 90D are radially spaced fromeach other and positioned longitudinally between electrode contacts 90Aand 90B. Each of the four electrode contacts may be operatedindependently via four separate conductors (four filar) in the lead body62.

With specific reference to FIGS. 27B-27G, each includes a top view (leftside) to schematically illustrate the electrical field or activatingfunction (labeled E), and an end view (right side) to schematicallyillustrate the area of the nerve effectively stimulated (labeled S) andthe area of the nerve effectively not stimulated (labeled NS).Electrodes 90A-90D are labeled A-D for sake of simplicity only. Thepolarity of the electrodes is also indicated, with each of the cathodesdesignated with a negative sign (−) and each of the anodes designatedwith a positive sign (+).

With reference to FIG. 27B, a tripolar transverse guarded cathodearrangement is shown with electrodes C and D comprising cathodes andelectrodes A and B comprising anodes, thus stimulating the entirecross-section of the nerve.

With reference to FIG. 27C, a bipolar diagonal arrangement is shown withelectrode C comprising a cathode and electrode A comprising an anode,wherein the fascicles that are stimulated may comprise superiorfascicles of the hypoglossal nerve, and the fascicles that are notstimulated may comprise inferior fascicles of the hypoglossal nerve(e.g., fascicles that innervate the intrinsic muscles of the tongue).

With reference to FIG. 27D, another bipolar diagonal arrangement isshown with electrode D comprising a cathode and electrode B comprisingan anode, wherein the fascicles that are stimulated may compriseinferior fascicles of the hypoglossal nerve.

With reference to FIG. 27E, a bipolar axial arrangement is shown withelectrode A comprising a cathode and electrode B comprising an anode,wherein the fascicles that are stimulated may comprise lateral fasciclesof the hypoglossal nerve.

With reference to FIG. 27F, a bipolar transverse arrangement is shownwith electrode C comprising a cathode and electrode D comprising ananode, wherein the fascicles that are stimulated may comprise medialfascicles of the hypoglossal nerve.

With reference to FIG. 27G, a modified tripolar transverse guardedcathode arrangement is shown with electrode C comprising a cathode andelectrodes A and B comprising anodes, thus stimulating the entirecross-section of the nerve with the exception of the inferior medialfascicles.

Description of Respiration Sensing Lead Anchoring Alternatives

With reference to the following figures, various additional oralternative anchoring features for the respiration sensing lead 70 areschematically illustrated. Anchoring the respiration sensing lead 70reduces motion artifact in the respiration signal and stabilizes thebio-impedance vector relative to the anatomy.

In each of the embodiments, by way of example, not limitation, therespiration sensing lead 70 includes a lead body 70 with a proximalconnector and a plurality of distal respiration sensors 74 comprisingring electrodes for sensing bio-impedance. The lead body 72 of therespiration sensing lead 70 may include a jacket cover containing aplurality of conductors 78, one for each ring electrode 74 requiringindependent control. Generally, the impedance electrodes 74 may comprisecurrent emitting electrodes and voltage sensing electrodes for detectingrespiration by changes in bio-impedance.

With reference to FIGS. 28-33, various fixation devices and methods areshown to acutely and/or chronically stabilize the respiratory sensinglead 70. With specific reference to FIG. 28, the INS 50 is shown in asubcutaneous pocket and the stimulation lead 60 is shown in asubcutaneous tunnel extending superiorly from the pocket. Therespiration sensing lead 70 is shown in a subcutaneous tunnelsuperficial to muscle fascia around the rib cage. A suture tab or ring270 may be formed with or otherwise connected to the distal end of thelead body 72. Near the distal end of the lead 70, a small surgicalincision may be formed to provide access to the suture tab 270 and themuscle fascia under the lead 70. The suture tab 270 allows the distalend of the lead 70 to be secured to the underlying muscle fascia bysuture or staple 272, for example, which may be dissolvable orpermanent. Both dissolvable and permanent sutures/staples provide foracute stability and fixation until the lead body 72 is encapsulated.Permanent sutures/staples provide for chronic stability and fixationbeyond what tissue encapsulation otherwise provides.

With reference to FIGS. 29A-29C, a fabric tab 280 may be used in placeof or in addition to suture tab 270. As seen in FIG. 29A, the fabric tab280 may be placed over a distal portion of the lead body 72, such asbetween two distal electrodes 74. A small surgical incision may beformed proximate the distal end of the lead 70 and the fabric tab 280may be placed over the over the lead body 72 and secured to theunderlying muscle fascia by suture or staple 282, for example, which maybe dissolvable or permanent, to provide acute and/or chronic stabilityand fixation. With reference to FIGS. 29B and 29C (cross-sectional viewtaken along line A-A), the fabric tab 280 may comprise a fabric layer(e.g., polyester) 284 to promote chronic tissue in-growth to the musclefascia and a smooth flexible outer layer (silicone or polyurethane) 286for acute connection by suture or staple 282.

With reference to FIG. 30, lead 70 includes a split ring 290 that may beformed with or otherwise connected to the distal end of the lead body72. The split ring 290 allows the distal end of the lead 70 to besecured to the underlying muscle fascia by suture or staple 292, forexample, which may be dissolvable or permanent. The ring 290 may beformed of compliant material (e.g., silicone or polyurethane) and mayinclude a slit 294 (normally closed) that allows the lead 70 to beexplanted by pulling the lead 70 and allowing the suture 292 to slipthrough the slit 294, or if used without a suture, to allow the ring todeform and slide through the tissue encapsulation. To further facilitateexplantation, a dissolvable fabric tab 282 may be used to acutelystabilize the lead 70 but allow chronic removal.

With reference to FIGS. 31A-31C, deployable anchor tines 300 may be usedto facilitate fixation of the lead 70. As seen in FIG. 31A, theself-expanding tines 300 may be molded integrally with the lead body 72or connected thereto by over-molding, for example. The tines 300 maycomprise relatively resilient soft material such as silicone orpolyurethane. The resilient tines 300 allow the lead 70 to be deliveredvia a tubular sheath or trocar 304 tunneled to the target sensing site,wherein the tines 300 assume a first collapsed delivery configurationand a second expanded deployed configuration. As seen in FIG. 31B, thetubular sheath or trocar 304 may be initially tunneled to the targetsite using an obtruator 306 with a blunt dissection tip 308. After thedistal end of the tubular sheath 304 has been tunneled into position byblunt dissection using the obtruator 306, the obtruator 306 may beremoved proximally from the sheath 304 and the lead 70 with collapsibletines 300 may be inserted therein. As seen in FIG. 31C, when the distalend of the lead 70 is in the desired position, the sheath 304 may beproximally refracted to deploy the tines 300 to engage the muscle fasciaand adjacent subcutaneous tissue, thus anchoring the lead 70 in place.

With reference to FIGS. 32A and 32B, an alternative deployable fixationembodiment is shown schematically. In this embodiment, self-expandingtines 310 are held in a collapsed configuration by retention wire 312disposed in the lumen of the lead body 72 as shown in FIG. 32A. Each ofthe tines 310 includes a hole 314 through which the retention wire 312passes to hold the tines 310 in a first collapsed delivery configurationas shown In FIG. 32A, and proximal withdrawal of the retention wire 314releases the resilient tines 310 to a second expanded deployedconfiguration as shown in FIG. 32B. The lead 70 may be tunneled to thedesired target site with the tines 310 in the collapsed configuration.Once in position, the wire 312 may be pulled proximally to release thetines 310 and secure the lead 70 to the underlying muscle fascia andadjacent subcutaneous tissue to establish fixation thereof.

With reference to FIGS. 33A and 33B, another alternative deployablefixation embodiment is shown schematically. In this embodiment,self-expanding structures such as one or more resilient protrusions 320and/or a resilient mesh 325 may be incorporated (either alone or incombination) into the distal end of the lead 70. By way of example, notlimitation, resilient protrusions 320 may comprise silicone orpolyurethane loops and resilient mesh 325 may comprise a polyesterfabric connected to or formed integrally with the lead body 72. Both theresilient protrusions 320 and the resilient mesh 325 may be delivered ina collapsed delivery configuration inside tubular sheath 304 as shown inFIG. 33A, and deployed at the desired target site by proximal retractionof the sheath 304 to release the self-expanding structures 320/325 to anexpanded deployed configuration as shown in FIG. 33B. Both the resilientprotrusions 320 and the resilient mesh 325 engage the underlying musclefascia through tissue encapsulation and adjacent subcutaneous tissues toprovide fixation of the lead 70 thereto.

Other fixation embodiments may be used as well. For example, thefixation element may engage the muscle fascia and adjacent subcutaneoustissues or may be embedded therein. To this end, the electrodes mayalternatively comprise intramuscular electrodes such as barbs or helicalscrews.

Description of Respiration Sensing Electrode Alternatives

A description of the various alternatives in number, spacing, anatomicallocation and function of the impedance electrodes follows. Generally, ineach of the following embodiments, the respiration sensing lead includesa lead body and a plurality of respiration sensors comprising ringelectrodes for sensing bio-impedance. The lead body may include aplurality of insulated conductors disposed therein, with one conductorprovided for each ring electrode requiring independent connection and/orcontrol. The impedance electrodes may comprise current emittingelectrodes and voltage sensing electrodes for detecting respiration bychanges in bio-impedance.

With reference to FIG. 34, the distal portion of a respiration sensinglead 70 is shown by way of example, not limitation. The respirationsensing lead 70 includes a lead body 72 with a proximal connector and aplurality of distal impedance electrodes 74. In this example, the leadbody 72 and electrodes 74 are cylindrical with a diameter of 0.050inches. The distal current-carrying electrode 74A may be 5 mm long andmay be separated from the voltage-sensing electrode 74B by 15 mm. Thedistal voltage sensing electrode may be 5 mm long and may be separatedfrom the proximal combination current-carrying voltage-sensing electrode74C by 100 mm. The proximal electrode 74C may be 10 mm long. Theproximal portion of the lead 70 is not shown, but would be connected tothe INS (not shown) as described previously. The lead body incorporatesa plurality of insulated electrical conductors (not shown), each ofwhich correspond to an electrode 74A-74C. The electrodes and conductorsmay be made of an alloy of platinum-iridium. The lead body 72 maycomprise a tubular extrusion of polyurethane, silicone, or aco-extrusion of polyurethane over silicone. The conductors may be formedof multi-filar wire coiled to provide extensibility for comfort anddurability under high-cycle fatigue.

With reference to FIGS. 35A-35E, the position of the electrodes 74 maybe characterized in terms of bio-impedance or bio-Z vectors. The bio-Zvector may be defined by the locations of the voltage-sensing electrodes(labeled V₁ & V₂). The voltage-sensing electrodes may be located oneither side of the current-carrying electrodes (labeled I₁ & I₂). Forexample, it is possible to locate either one or both of thevoltage-sensing electrodes between the current-carrying electrodes asshown in FIG. 35A (4-wire configuration (I₁-V₁-V₂-I₂)), and it ispossible to locate either one or both of the current-carrying electrodesbetween the voltage-sensing electrodes as shown in FIG. 35B (inverted4-wire configuration (V₁-I₁-I₂-V₂)). While at least two separateelectrodes (I₁ & I₂) are required to carry current and at least twoseparate electrodes (V₁ & V₂) are required to measure voltage, it ispossible to combine the current carrying and voltage sensing functionsin a common electrode. Examples of combining voltage sensing and currentcarrying electrodes are shown in FIGS. 35C-35E. FIG. 35C (2-wireconfiguration (I₁V₁-I₂V₂)) shows combination electrode I₁V₁ and I₂V₂where each of these electrodes is used to carry current and sensevoltage. FIG. 35D (3-wire configuration (I₁-V₁-I₂V₂)) and 35E (inverted3-wire configuration (V₁-I₁-I₂V₂)) show combination electrode I₂V₂ whichis used to carry current and sense voltage.

With reference to FIG. 36, insulative material such as strips 73 maycover one side of one or more electrodes 74A-74D to provide directionalcurrent-carrying and/or voltage-sensing. The insulative strips maycomprise a polymeric coating (e.g., adhesive) and may be arranged toface outward (toward the dermis) such that the exposed conductive sideof each electrode 74 faces inward (toward the muscle fascia and thoraciccavity). Other examples of directional electrodes would be substantiallytwo-dimensional electrodes such as discs or paddles which are conductiveon only one side. Another example of a directional electrode would be asubstantially cylindrical electrode which is held in a particularorientation by sutures or sutured wings. Another example of adirectional electrode would be an electrode on the face of the implantedpulse generator. It would likely be desirable for the pulse generator tohave a non-conductive surface surrounding the location of the electrode.

In addition to the cylindrical electrodes shown, other electrodeconfigurations are possible as well. For example, the electrodes may bebi-directional with one planar electrode surface separated from anotherplanar electrode surface by insulative material. Alternatively or incombination, circular hoop electrodes may be placed concentrically on aplanar insulative surface. To mitigate edge effects, each electrode maycomprise a center primary electrode with two secondary side electrodesseparated by resistive elements and arranged in series. An alternativeis to have each primary current-carrying electrode connected by aresistive element to a single secondary side electrode. The conductivehousing of the INS 50 may serve as an current-carrying electrode orvoltage-sensing electrode. Alternatively or in addition, an electrodemay be mounted to the housing of the INS 50.

Because bio-impedance has both a real and imaginary component, it ispossible to measure the bio-Z phase as well as magnitude. It may bepreferable to extract both magnitude and phase information from thebio-Z measurement because the movement of the lung-diaphragm-liverinterface causes a significant change in the phase angle of the measuredimpedance. This may be valuable because motion artifacts of other tissuehave less impact on the bio-Z phase angle than they do on the bio-Zmagnitude. This means the bio-Z phase angle is a relatively robustmeasure of diaphragm movement even during motion artifacts.

An example of a bio-Z signal source is a modulated constant-currentpulse train. The modulation may be such that it does not interfere withthe stimulation signal. For example, if the stimulation signal is 30 Hz,the bio-Z signal source signal may be modulated at 30 Hz such that bio-Zand stimulation do not occur simultaneously. The pulses in the pulsetrain may have a pulse width between 1 uS to 1 mS, such as 10 uS. Thepulses may be separated by a period of time roughly equal to the pulsewidth (i.e., on-time of the pulses). The number of pulses in a train maybe determined by a trade-off between signal-to-noise and powerconsumption. For example, no more than 100 pulses may be necessary inany given pulse train. The magnitude of current delivered during thepulse on-time may be between 10 uA and 500 uA, such as 50 uA.

Other wave forms of bio-Z source signal may be used, including, withoutlimitation, pulse, pulse train, bi-phasic pulse, bi-phasic pulse train,sinusoidal, sinusoidal w/ramping, square wave, and square w/ramping. Thebio-Z source signal may be constant current or non-constant current,such as a voltage source, for example. If a non-constant current sourceis used, the delivered current may be monitored to calculate theimpedance value. The current-carrying electrodes may have a singlecurrent source, a split-current source (one current source split betweentwo or more current-carrying electrodes), or a current mirror source(one current source that maintains set current levels to two or morecurrent-carrying electrodes). Different characteristics of the sensedsignal may be measured including, without limitation, magnitude, phaseshift of sensed voltage relative to the current source signal, andmulti-frequency magnitude and/or phase shift of the sensed signal.Multi-frequency information may be obtained by applying multiple signalsources at different frequencies or a single signal source whichcontains two or more frequency components. One example of a singlemulti-frequency source signal is a square wave current pulse. Theresultant voltage waveform would contain the same frequency componentsas the square wave current pulse which would allow extraction of Bio-Zdata for more than a single frequency.

With reference to FIG. 37, the bio-Z vector may be oriented with regardto the anatomy in a number of different ways. For example, using theelectrode arrangement illustrated in FIG. 34 and the anatomicalillustration in FIG. 37, the bio-Z vector may be arranged such that theproximal combination electrode is located just to the right of and abovethe xiphoid below the pectoral muscle between the 5^(th) and 6^(th) ribsand the distal current-carrying electrode is located mid-lateral betweenthe 7^(th) and 8^(th) ribs, with the distal voltage-sensing electrodepositioned between the 6^(th) and 7^(th) ribs 10 mm proximal of thedistal current-carrying electrode. This arrangement places theelectrodes along the interface between the right lung, diaphragm andliver on the right side of the thoracic cavity. The lung-diaphragm-liverinterface moves relative to the bio-Z vector with every respiratorycycle. Because the lung has relatively high impedance when inflated andthe liver has relatively low impedance due to the conductivity of bloodtherein, this bio-Z vector arrangement across the lung-diaphragm-liverinterface provides for a strong respiratory signal that is indicative ofchanges between inspiration and expiration. In addition, because theheart is situated more on the left side, positioning the bio-Z vector onthe right side reduces cardiac artifact. The net result is a bio-Zvector that provides an excellent signal-to-noise ratio.

A variety of different bio-Z vector orientations relative to the anatomymay be employed. Generally, bio-Z vectors for monitoring respiration maybe located on the thorax. However, bio-Z electrodes located in the headand neck may also be used to define respiratory bio-Z vectors. By way ofexample, not limitation, the bio-Z vector may be arrangedtransthoracically (e.g., bilaterally across the thorax), anteriorly onthe thorax (e.g., bilaterally across the thoracic midline), across thelung-diaphragm-liver interface, perpendicular to intercostal muscles,between adjacent ribs, etc. A single bio-Z vector may be used, ormultiple independent vectors may be used, potentially necessitatingmultiple sensing leads. One or more bio-Z sub-vectors within a givenbio-Z vector may be used as well.

With reference to FIGS. 38A-38C, thoracic locations defining examples ofbio-Z vectors are shown schematically. FIG. 38A is a frontal view of thethorax, FIG. 38B is a right-side view of the thorax, and FIG. 38C is aleft-side view of the thorax. In each of FIGS. 38A-38C, the outline ofthe lungs and upper profile of the diaphragm are shown. As mentionedpreviously, a bio-Z vector may be defined by the locations of thevoltage-sensing electrodes. Thus, FIGS. 38A-38C show locations forvoltage sensing electrodes which would define the bio-Z vector.

By way of example, not limitation, the following bio-Z vectors may beeffective for monitoring respiration and/or for measuring artifacts forsubsequent removal of the artifact from the respiration signal. VectorC-G is across the upper left and upper right lobes of the lungs, andprovides a good signal of ribcage expansion with moderate cardiacartifact. Vector D-F is a short-path version of C-G that provides a goodrespiratory signature largely correlated with ribcage expansion, withless cardiac artifact than C-G, but may be sensitive to movement of armsdue to location on pectoral muscles. Vector C-D is a short-pathipsilateral vector of the upper right lung that may be sensitive to armmovement but has less cardiac artifact. Vector B-H is a transversevector of thoracic cavity that captures the bulk of the lungs anddiaphragm movement, but may have relatively large cardiac artifactVector A-E is an ipsilateral vector across the lung-diaphragm-liverinterface. Because the liver is higher in conductivity and has adifferent impedance phase angle than the lung, vector A-E1 yields a goodsignal on both bio-Z magnitude and phase with limited cardiac artifactVector B-K is an ipsilateral vector across the lung-diaphragm-liverinterface that is substantially between a common set of ribs with acurrent path that is mostly perpendicular to the intercostal muscles.Because resistivity of muscle is much higher perpendicular to the muscledirection than parallel, vector B-K reduces current-shunting through themuscle which otherwise detracts from the signal of thelung-diaphragm-liver interface. Vector A-K is an ipsilateral vectoracross the lung-diaphragm-liver interface similar to vector A-E1 but ismore sensitive to movement of the lung-diaphragm-liver interface than tochanges in resistivity of the lung-diaphragm-liver interface due toinspired air volume and is thus a good indicator of diaphragm movementVector B-E1 is a vector across the middle and lower right lung and isgood for detecting diaphragm movement with little cardiac artifact.Vector C-E1 is a vector across the upper and middle right lung and isalso good for detecting diaphragm movement with little cardiac artifactVector D-E1 is a vector across the upper right lung with little cardiacartifact Vector A-D is an ipsilateral across a substantial portion ofthe right lung and diaphragm with little cardiac artifact, but may besusceptible to motion artifact due to arm movement. Vector E1-E2 is avector across the heart and provides a good cardiac signal that may beused for removing cardiac artifact from a respiratory signal. VectorE2-J is a vector across the lung-diaphragm-stomach interface thatprovides a good measure of diaphragm movement using bio-Z phase vs.magnitude because the stomach has almost no capacitive component andgenerally low conductivity.

The respiratory bio-Z signal is partly due to the resistivity changewhich occurs when air infuses lung tissue, partly due to the relativemovement of electrodes as the rib cage expands, and partly due to thedisplacement of other body fluids, tissue and organs as the lungs movealong with the ribcage and diaphragm. As described above, each vectormeasures certain of these changes to different extents. It may bedesirable, therefore, to combine vectors which have complementaryinformation or even redundant information to improve the respiratoryinformation of the bio-Z signal. To this end, multiple vectors may beused. For example, one vector may be used to sense changes in thelung-diaphragm-liver interface and a second vector may be used to detectchanges (e.g., expansion, contraction) of the lung(s). Examples of theformer include A-K, B-K, A-E1, B-E1, and A-B. Examples of the laterinclude D-F, B-D, C-G, D-E1, and C-E1. Note that some vectorcombinations which share a common vector endpoint such as A-E1, D-E1 andB-E1, B-D may use a common electrode which would simplify therespiratory sensing lead or leads.

An advantage of using the lung-diaphragm-liver interface vector is thatit provides a robust signal indicative of the movement of the diaphragmthroughout the respiratory cycle. The liver is almost two times moreelectrically conductive than lung tissue so a relatively large bio-Zsignal can be obtained by monitoring the movement of thelung-diaphragm-liver interface. Because the liver functions to filterall the blood in the body, the liver is nearly completely infused withblood. This helps to dampen out the cardiac artifact associated with thepulsatile flow of the circulatory system. Another advantage of thislocation is that vectors can be selected which avoid significant currentpath through the heart or major arteries which will help reduce cardiacartifact.

It is worth noting that diaphragm movement is not necessarilysynchronous with inspiration or expiration. Diaphragm movement typicallycauses and therefore precedes inspiration and expiration. Respiratorymechanics do allow for paradoxical motion of the ribcage and diaphragm,so diaphragm movement is not necessarily coincident with inspiration.During REM sleep, the diaphragm is the dominant respiratory driver andparadoxical motion of the ribs and diaphragm can be problematic,especially if movement of the ribcage is being relied upon as aninspiratory indicator. Monitoring the diaphragm for pre-inspiratorymovement becomes especially valuable under these circumstances. Bio-Zmonitoring of the diaphragm can be used as a more sophisticatedindicator of impending inspiration rather than the antiquated approachof desperately trying to identify and respond to inspiration inpseudo-real time based on sensors which are responding tocharacteristics of inspiration.

For purposes of monitoring respiration, it is desirable to minimizeshunting of the electrical current through tissues which are not ofinterest. Shunting may result in at least two problems: reduced signalfrom the lungs; and increased chance of artifacts from the shuntedcurrent path. Skeletal muscle has non-isotropic conductivity. Themuscle's transverse resistivity (1600 ohm-cm) is more than 5 times itslongitudinal resistivity (300 ohm-cm). In order to minimize the adverseeffect of shunting current, it is desirable to select bio-Z sensingvectors which are perpendicular to muscle structure if possible. Onesuch example is to locate two or more electrodes of a bio-Z sensingarray substantially aligned with the ribs because the intercostalmuscles are substantially perpendicular to the ribs.

Description of Respiration Signal Processing

With reference to FIG. 39, the neurostimulation system described hereinmay operate in a closed-loop process 400 wherein stimulation of thetargeted nerve may be delivered as a function of a sensed feedbackparameter (e.g., respiration). For example, stimulation of thehypoglossal nerve may be triggered to occur during the inspiratory phaseof respiration. Alternatively, the neurostimulation system describedherein may operate in an open-loop process wherein stimulation isdelivered as a function of preset conditions (e.g., historical averageof sleeping respiratory rate).

With continued reference to FIG. 39, the closed-loop process 400 mayinvolve a number of generalized steps to condition the sensed feedbackparameter (e.g., bio-Z) into a useable trigger signal for stimulation.For example, the closed-loop process 400 may include the initial step ofsensing respiration 350 using bio-Z, for example, and optionally sensingother parameters 360 indicative of respiration or other physiologicprocess. The sensed signal indicative of respiration (or otherparameter) may be signal processed 370 to derive a usable signal anddesired fiducials. A trigger algorithm 380 may then be applied to theprocessed signal to control delivery of the stimulation signal 390.

With reference to FIG. 40, the signal processing step 370 may includegeneral signal amplification and noise filtering 372. The step ofamplification and filtering 372 may include band pass filtering toremove DC offset, for example. The respiratory waveform may then beprocessed to remove specific noise artifacts 374 such as cardiac noise,motion noise, etc. A clean respiratory waveform may then be extracted376 along with other waveforms indicative of specific events such asobstructive sleep apnea (OSA), central sleep apnea (CSA), hypopnea,sleep stage, etc. Specific fiducial points may then be extracted andidentified (e.g., type, time, and value).

The step of removing specific noise artifacts 374 may be performed in anumber of different ways. However, before signal processing 374, bothcardiac and motion noise artifact may be mitigated. For example, bothcardiac and motion noise artifact may be mitigated prior to signalprocessing 374 by selection of bio-Z vectors that are less susceptibleto noise (motion and/or cardiac) as described previously. In addition,motion artifact may be mitigated before signal processing 374 byminimising movement of the sensing lead and electrodes relative to thebody using anchoring techniques described elsewhere herein. Furthermore,motion artifact may be mitigated prior to signal processing 374 byminimizing relative movement between the current-carrying electrodes andthe voltage-sensing electrodes, such as by using combinedcurrent-carrying and voltage-sensing electrodes.

After cardiac and motion artifact has been mitigated using thepre-signal processing techniques described above, both cardiac andmotion artifact may be removed by signal processing 374.

For example, the signal processing step 374 may involve the use of a lowpass filter (e.g., less than 1 Hz) to remove cardiac frequency noisecomponents which typically occur at 0.5 to 2.0 Hz, whereas restingrespiration frequency typically occurs below 1.0 Hz.

Alternatively, the signal processing step 374 may involve the use of aband pass or high pass filter (e.g., greater than 1 Hz) to obtain acardiac sync signal to enable removal of the cardiac noise from thebio-Z signal in real time using an adaptive filter, for example.Adaptive filters enable removal of noise from a signal in real time, andan example of an adaptive filter is illustrated in FIG. 41. To removecardiac artifact from the bio-Z signal which contains both cardiac noisen(k) and respiratory information s(k), a signal n′(k) that representscardiac noise is input to the adaptive filter and the adaptive filteradjusts its coefficients to reduce the value of the difference betweeny(k) and d(k), removing the noise and resulting in a clean signal ine(k). Notice that in this application, the error signal actuallyconverges to the input data signal, rather than converging to zero.

Another signal processing technique to remove cardiac noise is tocombine signals from two or more bio-Z vectors wherein respiration isthe predominate signal with some cardiac noise. This may also be used toreduce motion artifact and other asynchronous noise. Each of the two ormore signals from different bio-Z vectors may be weighted prior tocombining them into a resultant signal Vw(i). If it is assumed that (a)the respiratory bio-impedance is the largest component in each measuredvector, (b) the non-respiratory signal components in one vector aresubstantially independent of the non-respiratory components in the othervector, and (c) the ratio of the non-respiratory component to therespiratory components in one vector is substantially equal to the sameratio in the other vector, then a simple weighting scheme may be usedwherein each signal is divided by it's historic peak-to-peak magnitudeand the results are added. For example, if M_(A)=historical averagepeak-to-peak magnitude of signal from vector A, Mg=historical averagepeak-to-peak magnitude of signal from vector B, V_(A)(i)=data point (i)from vector A, V_(B)(i)=data point (i) from vector B, then the resultantsignal V_(W)(i) (i.e., weighted average of A & B for data point (i)) maybe expressed as V_(w)(i)=V_(A)(i)/M_(A)+V_(B)(i)/M_(B).

Yet another signal processing technique for removing cardiac noise is tosubtract a first signal that is predominantly respiration from a secondsignal that is predominantly cardiac. For example, the first signal maybe from a predominantly respiratory bio-Z vector (e.g., vector B-H) withsome cardiac noise, and the second signal may be from a predominantlycardiac bio-Z vector (e.g., vector E1-E2) with some respiration signal.Each of the two signals from the different bio-Z vectors may be weightedprior to subtracting them. The appropriate weighting may be determined,for example, by calculating the power density spectra in the range of2-4 Hz for a range of weighted differences across at least severalrespiratory cycles. A minimum will occur in the power density spectrafor the weighted averages which are sufficiently optimal.

Motion artifact may be removed by signal processing 374 as well. Motionartifact may be identified and rejected using signal processingtechniques such as monitoring voltage magnitude, testing the correlationof magnitude and phase, and/or testing correlation at two or morefrequencies. Motion artifacts may cause a large change in measuredbio-impedance. A typical feature of motion artifacts is that the voltageswings are much larger than respiration. Another feature is that thevoltage changes are highly erratic. Using these characteristics, whichwill be described in more detail below, motion artifact may be removedfrom the respiration signal.

The step of extracting waveforms indicative of respiration and otherevents 374 may be better explained with reference to FIGS. 42-46 whichschematically illustrate various representative unfiltered bio-Zsignals. FIG. 42 schematically illustrates a bio-Z signal 420 withrepresentative signatures indicative normal respiration (i.e., eventfree) during an awake period 422 and a sleeping period 424. FIG. 43schematically illustrates a bio-Z signal 430 with representativesignatures indicative of normal respiration during sleeping periods 424interrupted by a period of motion 432 (i.e., motion artifact). FIG. 44schematically illustrates a bio-Z signal 440 with representativesignatures indicative of normal respiration during a sleeping period 424followed by periods of hypopnea (HYP) 442 and recovery 444. FIG. 45schematically illustrates a bio-Z signal 450 with representativesignatures indicative of normal respiration during a sleeping period 424followed by periods of obstructive sleep apnea (OSA) 452 and recovery454 (which typically includes an initial gasp 456). FIG. 46schematically illustrates a bio-Z signal 460 with representativesignatures indicative of normal respiration during a sleeping period 424followed by periods of central sleep apnea (CSA) 462 (which typicallyincludes a cessation in breathing 468) and recovery 464.

The step of extracting 374 waveform data indicative of an awake period422 vs. a sleep period 424 from a bio-Z signal 420 may be explained inmore detail with reference to FIG. 42. In addition, the step offiltering 372 waveform data indicative of motion 432 from a bio-Z signal430 may be explained in more detail with reference to FIG. 43. One wayto determine if a person is awake or moving is to monitor thecoefficient of variation (CV) of sequential peak-to-peak (PP) magnitudesover a given period of time. CV is calculated by taking the standarddeviation (or a similar measure of variation) of the difference betweensequential PP magnitudes and dividing it by the average (or a similarstatistic) of the PP magnitudes. N is the number of respiratory cycleswhich occur in the selected period of time.

The CV may be calculated as follows:

${CV} = \frac{{sd}({dPP})}{\overset{\_}{PP}}$ Where:${{sd}({dPP})} = \sqrt{\frac{\sum\limits_{i = 1}^{N}\; \left( {{dPP}_{i} - \overset{\_}{dPP}} \right)}{\left( {N - 1} \right)}}$$\overset{\_}{dPP} = \frac{\sum\limits_{i = 1}^{N}\; \left( {dPP}_{i} \right)}{(N)}$dPP_(i) = PP_(i + 1) − PP_(i)$\overset{\_}{PP} = \frac{\sum\limits_{i = 1}^{N}\; \left( {PP}_{i} \right)}{(N)}$

Generally, if the CV is greater than 0.20 over a one minute period thenperson is awake. Also generally, if the CV is less than 0.20 over aone-minute period then person is asleep. These events may be flagged forthe step of fiducial extraction 378 wherein data (e.g., event duration,CV, PP range, PPmin, PPmax, etc.) may be time stamped and stored with anevent identifier. If CV is greater than 1.00 over a 20 second periodthen body movement is affecting the bio-Z signal. By way of example, notlimitation, if body movement is detected, then (a) stimulation may bedelivered in an open loop fashion (e.g., based on historical respiratorydata); (b) stimulation may be delivered constantly the same or lowerlevel; or (c) stimulation may be turned off during the period ofmovement. The selected stimulation response to detected movement may bepreset by the physician programmer or by the patient control device.Other stimulation responses may be employed as will be describedhereinafter.

In each of FIGS. 44-46, maximum and minimum peak-to-peak magnitudes(PPmax and PPmin) may be compared to distinguish hypopnea (HYP),obstructive sleep apnea (OSA), and central sleep apnea (CSA) events.Generally, PP values may be compared within a window defined by theevent (HYP, OSA, CSA) and the recovery period thereafter. Alsogenerally, the window in which PP values are taken excludes transitionalevents (e.g., gasp 456, 466). As a general alternative, peak-to-peakphases may be used instead of peak-to-peak magnitude. The hypopnea andapnea events may be flagged for the step of fiducial extraction 378wherein data (e.g., event duration, CV, PP range, PPmin, PPmax, etc.)may be time stamped and stored with an event identifier.

A typical indication of hypopnea (HYP) and apnea (OSA, CSA) events is arecurrent event followed by a recovery. The period (T) of each event(where PP oscillates between PPmax and PPmin and back to PPmax) may beabout 15 to 120 seconds, depending on the individual. The largest PPvalues observed during hypopneas and apneas are usually between 2 and 5times larger than those observed during regular breathing 424 duringsleep. The ratio of the PPmax to PPmin during recurrent hypopnea andapnea events is about 2 or more. During the event and recovery periods(excluding transitional events), PP values of adjacent respiratorycycles do not typically change abruptly and it is rare for the change inPP amplitude to be more than 50% of PPmax. One exception to thisobservation is that some people gasp 456, 466 (i.e., transitional event)as they recover from a CSA or OSA event.

The ratio of successive PP magnitudes during normal (non-event) sleep424 is mostly random. The ratio of successive PP magnitudes during apneaand hypopnea events will tend to be a non-random sequence due to theoscillatory pattern of the PP values. Recurrent apneas and hypopneas maybe diagnosed by applying a statistical test to the sequence ofsuccessive PP ratios.

The step of extracting 374 waveform data indicative of an hypopnea event442 from a bio-Z signal 440 may be explained in more detail withreference to FIG. 44. The ratio of PPmax to PPmin during recurrenthypopneas is typically between 2 and 5. This is in contrast to CSA'swhich have very small PPmin due to the complete cessation of breathing.This results in CSA's having PPmax to PPmin ratios larger than 5.Accordingly, hypopnea events may be detected, identified and flagged forthe step of fiducial extraction 378 wherein data (e.g., event duration,CV, PP range, PPmin, PPmax, etc.) may be time stamped and stored with anevent identifier.

The step of extracting 374 waveform data indicative of an OSA event 452from a bio-Z signal 450 may be explained in more detail with referenceto FIG. 45. The sharp change 456 in the bio-Z respiratory magnitude dueto OSA is typically in the range of 1 to 4 times the magnitude of thepeak-to-peak respiratory cycle magnitude. The sharp change 456 typicallytakes less than 5 seconds to occur. OSA tends to occur in a recurringsequence where the period (T) between sequential events is between 15and 120 seconds. A one-minute period is commonly observed. According tothese characteristics, OSA events may be detected, identified andflagged for the step of fiducial extraction 378 wherein data (e.g.,event duration, CV, PP range, PPmin, PPmax, etc.) may be time stampedand stored with an event identifier.

The step of extracting 374 waveform data indicative of a CSA event 462from a bio-Z signal 460 may be explained in more detail with referenceto FIG. 46. The behavior of the Bio-Z signal throughout recurrent CSAevents differ from other hypopnea and OSA in three ways. First, duringCSA there is complete cessation of respiratory activity which results ina flat Bio-Z signal. This means the ratio of PPmax to PPmin is typicallygreater than 5 during recurrent CSA events. The duration of theestimated respiratory cycle may also be used to distinguish between CSAfrom OSA and hypopnea. The lack of respiratory activity during CSAresults in an inflated estimate for the respiratory cycle period. The PPtypically does not vary by more than 50% for successive cycles. Therespiratory cycle duration during a CSA event is more than twice as longas the duration of the respiratory cycles preceding the CSA event.Second, during CSA the Bio-Z magnitude will drift outside the PPmagnitude range observed during respiration. It has been observed thatwith the onset of central sleep apnea (CSA) the magnitude and phase ofthe Bio-Z signal settle to a steady-state value outside the peak-to-peakrange observed during the normal respiratory cycle during sleep. Third,upon arousal from CSA a person will typically gasp. This gasp results ina large PP. The PP of the first respiratory cycle following the CSAevent and the PP observed during the CSA (which is essentially noise)will exceed 50% of PPmax.

With continued reference to FIG. 46, the flat portions 468 of the datatraces are periods of respiratory cessation. Upon arousal the subjectgasps 466 and the raw bio-Z signal resumes cyclic oscillation above thestatic impedance level observed during CSA. According to thesecharacteristics, CSA events may be detected, identified and flagged forthe step of fiducial extraction 378 wherein data (e.g., event duration,CV, PP range, PPmin, PPmax, etc.) may be time stamped and stored with anevent identifier.

The step of extracting 374 waveform data indicative of sleep stage(e.g., rapid eye movement (REM) sleep vs. no-rapid eye movement (NREM)sleep) may be performed by comparing the phase difference between afirst vector and a second vector wherein the first bio-Z vector is alongthe lung-diaphragm-liver interface (e.g., vector A-K or vector B-K) andthe second bio-Z vector is about the lung(s). Examples of the firstbio-Z vector include A-K, B-K, A-E1, B-E1, and A-B. Examples of thesecond bio-Z vector include D-F, B-D, C-G, D-E1, and C-E1. Note thatsome vector combinations which share a common vector endpoint such asA-E1, D-E1 and B-E1, B-D may use a common electrode and to simplify therespiratory sensing lead or leads. Typically, during NREM sleep, the twovectors are substantially in phase. During REM sleep, the diaphragm isthe primary respiratory driver and a common consequence is paradoxicalmotion of the ribcage and diaphragm (i.e., the two vectors aresubstantially out of phase). This characteristic would allow for aneffective monitor of a person's ability to reach REM sleep. Accordingly,REM and NREM sleep stages may be detected, identified, and flagged forthe step of fiducial extraction 378 wherein characteristic data (e.g.,event duration, phase, etc.) may be time stamped and stored with anevent identifier.

An alternative method of detecting an OSA event is to make use of asplit current electrode arrangement as shown in FIG. 47 which shows thepositions of three electrodes on the subject. Electrode A may be abovethe zyphoid, electrode B may be just above the belly button, andelectrode C may be on the back a couple of inches below electrode A.Electrodes A and B are connected to a common constant current sourcethrough resistors R1 and R2. The voltage measured across the currentsource is a measure of the bio-impedance during normal respiration. Thevoltage across R1 is an indicator of the paradoxical motion associatedwith apnea. An unbalanced current split between R1 and R2 resulting inlarge bio-Z voltage swings is indicative of OSA. During normalrespiration or even very deep breaths there is almost no effect on theapnea detection channel. Accordingly, OSA events may be detected,identified, and flagged for the step of fiducial extraction 378 whereincharacteristic data (e.g., event duration, voltage swing magnitude,etc.) may be time stamped and stored with an event identifier.

Generally, the extracted 378 waveform and event data may be used fortherapy tracking, for stimulus titration, and/or for closed loop therapycontrol. For example, data indicative of apneas and hypopneas (or otherevents) may be stored by the INS 50 and/or telemetered to the patientcontrolled 40. The data may be subsequently transmitted or downloaded tothe physician programmer 30. The data may be used to determinetherapeutic efficacy (e.g., apnea hypopnea index, amount of REM sleep,etc.) and/or to titrate stimulus parameters using the physicianprogrammer 30. The data may also be used to control stimulus in a closedloop fashion by, for example, increasing stimulus intensity duringperiods of increased apnea and hypopnea occurrence or decreasingstimulus intensity during periods of decreased apnea and hypopneaoccurrence (which may be observed if a muscle conditioning effect isseen with chronic use). Further, the data may be used to turn stimuluson (e.g., when apnea or hypopnea events start occurring or when motionartifact is absent) or to turn stimulus off (e.g., when no apnea orhypopnea events are occurring ever a present time period or when motionartifact is predominant).

Description of Stimulus Trigger Algorithms

As mentioned previously with reference to FIG. 39, the neurostimulationsystem described herein may operate in a closed-loop process wherein thestep of delivering stimulation 390 to the targeted nerve may be afunction of a sensed feedback parameter (e.g., respiration). Forexample, stimulation of the hypoglossal nerve may be triggered to occurduring the inspiratory phase of respiration. In a health human subject,the hypoglossal nerve is triggered about 300 mS before inspiration.Accordingly, a predictive algorithm may be used to predict theinspiratory phase and deliver stimulation accordingly. FIG. 48schematically illustrates a system 480 including devices, data andprocesses for implementing a self-adjusting predictive triggeralgorithm.

The system components 482 involved in implementing the algorithm mayinclude the physician programmer (or patient controller), INS andassociated device memory, and the respiratory sensor(s). The sensors anddevice memory are the sources of real-time data and historical fiducialdata which the current algorithm uses to generate a stimulation triggersignal. The data 484 utilized in implementing the algorithm may includepatient specific data derived from a sleep study (i.e., PSG data), datafrom titrating the system post implantation, and historic and real-timerespiratory data including respiratory and event fiducials. Theprocesses 486 utilized in implementing the algorithm may includeproviding a default algorithm pre-programmed in the INS, patientcontroller or physician programmer, modifying the default algorithm, andderiving a current algorithm used to generate a trigger signal 488.

More specifically, the processes 486 utilized in implementing apredictive trigger algorithm may involve several sub-steps. First, adefault algorithm may be provided to predict onset of inspiration fromfiducial data. Selecting an appropriate default algorithm may depend onidentifying the simplest and most robust fiducial data subsets whichallow effective prediction of onset. It also may depend on a reliablemeans of modifying the algorithm for optimal performance. Second,modification of the default algorithm may require a reference datum. Thereference datum may be the estimated onset for past respiratory cycles.It is therefore useful to precisely estimate inspiratory onset forprevious respiratory cycles from historical fiducial data. Thisestimation of inspiratory onset for previous respiratory cycles may bespecific to person, sensor location, sleep stage, sleep position, or avariety of other factors. Third, the current algorithm may be derivedfrom real-time and historical data to yield a stimulation trigger signal488.

With reference to FIG. 48, a self adjusting predictive algorithm may beimplemented in the following manner.

The Programmer block is illustrates means by which PSG-derived data maybe uploaded into the device.

The Sensors and Device Memory block includes the sources of real-timedata and historical fiducial variables which the current algorithm usesto generate a stimulation trigger signal.

The Patient PSG Titration Data block includes conventionalpolysomnographic (PSG) data obtained in a sleep study. A self-adjustingpredictive algorithm utilizes a reference datum to which the algorithmcan be adjusted. Onset may be defined as onset of inspiration asmeasured by airflow or pressure sensor used in a sleep study, forexample. Estimated Onset may be defined as an estimate of Onsetcalculated solely from information available from the device sensors andmemory. To enable the predictive algorithm to be self-adjusting, eitherOnset or Estimated Onset data is used. During actual use, the implanteddevice will typically not have access to Onset as that would requireoutput from an airflow sensor. The device then may rely on an estimateof Onset or Estimated Onset. The calibration of Estimated Onset to Onsetmay be based on PSG data collected during a sleep study. The calibrationmay be unique to a person and/or sleep stage and/or sleep positionand/or respiratory pattern.

The Historical Fiducial Variables block represents the HistoricalFiducial Variables (or data) which have been extracted from the bio-Zwaveform and stored in the device memory. This block assumes that theraw sensor data has been processed and is either clean or has beenflagged for cardiac, movement, apnea or other artifacts. Note thatfiducial data includes fiducials, mathematical combinations of fiducialsor a function of one or more fiducials such as a fuzzy logic decisionmatrix.

The Real-Time Data and Historical Fiducial Variables block incorporatesall the information content of the Historical Fiducial Variables blockand also includes real-time bio-Z data.

The Default Algorithm block represents one or more pre-set triggeralgorithms pre-programmed into the INS or physician programmer. Thedefault algorithm used at a specific point in time while deliveringtherapy may be selected from a library of pre-set algorithms. Theselection of the algorithm can be made automatically by the INS basedon: patient sleep position (position sensor), heart rate (detectablethrough the impedance measuring system) or respiration rate. Clinicalevidence supports that the algorithm used to predict the onset ofinspiration may be dependant on sleep position, sleep state or otherdetectable conditions of the patient.

The Modify Algorithm block represents the process of modifying theDefault Algorithm based on historical data to yield the CurrentAlgorithm. Once the calibration of Estimated Onset to Onset is residentin the device memory it can be used to calculate Estimated Onset forpast respiratory cycles from Fiducial Variables. The variable used torepresent the Estimated Onset will be TEST or TEST(i) where the “i”indicates the cycle number. Note that Estimated Onset is calculated forpast respiratory cycles. This means that sensor fiducial variables whicheither proceed or follow each Onset event may be used to calculate theEstimated Onset.

The Current Algorithm block represents the process of using the ModifiedDefault Algorithm to predict the next inspiratory onset (PredictedOnset). The Predicted Onset for the next respiratory cycle may becalculated from real-time data and historical fiducial variables. Thecalculation may be based on the Modified Default Algorithm. Modificationof the Modified Default Algorithm to derive the Current Algorithm may bedependent on the calibration of Estimated Onset to Onset which was inputfrom the physician programmer and may be based on comparison ofreal-time bio-Z data to data collected during a PSG titration study. TheCurrent Algorithm may use historic and/or real-time sensor fiducialvariables to predict the next onset of inspiration. This predicted onsetof inspiration may be referred to as Predicted Onset. The variable usedto represent Predicted Onset may be TPRED or TPRED(i) where the “i”indicates the respiratory cycle.

The Stimulation Trigger Signal block represents the Current Algorithmgenerating a trigger signal which the device uses to trigger stimulationto the hypoglossal nerve.

FIG. 49 is a table of some (not all) examples of waveform fiducialswhich can be extracted from each respiratory cycle waveform. For eachfiducial there is a magnitude value and a time of occurrence. Eachwaveform has a set of fiducials associated with it. As a result,fiducials may be stored in the device memory for any reasonable numberof past respiratory cycles. The values from past respiratory cycleswhich are stored in device memory are referred to as Historical FiducialVariables.

The graphs illustrated in FIG. 50 are examples of fiducials marked onbio-Z waveforms. The first of the three graphs illustrate thebio-impedance signal after it has been filtered and cleared of cardiacand motion artifacts. The first graph will be referred to as the primarysignal. The second graph is the first derivative of the primary signaland the third graph is the second derivative of the primary signal. Eachgraph also displays a square wave signal which is derived from airflowpressure. The square wave is low during inspiration. The falling edge ofthe square wave is onset of inspiration.

Due to the fact that it may be difficult to identify onset ofinspiration in real-time from respiratory bio-impedance, a goal is toconstruct an algorithm which can reliably predict onset of inspiration“T” for the next respiratory cycle from information available from thecurrent and/or previous cycles. A reliable, distinct and known referencepoint occurring prior to onset of inspiration, “T”, is “A”, the peak ofthe primary signal in the current cycle. As can be seen in FIG. 50, theupper peak of the bio-Z waveform “A” approximately corresponds to theonset of expiration “O”. A dependent variable t_(T-PK) is created torepresent the period of time between the positive peak of the primarysignal for the current cycle, t.Vmax(n), indicated by “A_(n),” on thegraph, and onset of inspiration for the next cycle, t.onset(n+1),indicated by “T” on the graph. The variable t_(T-PK) may be defined as:

t _(T-PK) =t.onset(n+1)−t.Vmax(n)

Note that t.Vmax could be replaced by any other suitable fiducial indefining a dependent variable for predicting onset.

A general model for a predictive algorithm may be of the following form:

t _(T-PK) =f(fiducials extracted from current and/or previous cycles)

A less general model would be to use a function which is a linearcombination of Fiducial Variables and Real-Time Data.

The following fiducials may be both highly statistically significant andpractically significant in estimating T:

t.Vmax(n)=the time where positive peak occurs for the current cycle;

t.dV.in(n)=the time of most positive 1^(st) derivative duringinspiration for the current cycle; and

t.Vmax(n−1)=the time of positive peak for the previous cycle.

This model can be further simplified by combining the variables asfollows:

Δt.pk(n)=t.Vmax(n)−t.Vmax(n−1)

Δt.in(n)=t.Vmax(n)−t.dV.in(n)

Either Δt.pk(n) or Δt.in(n) is a good predictor of Onset.

The following example uses Δt.pk(n). The time from a positive peak untilthe next inspiration onset can be estimated by:

T _(pred) =t.Vmax(n)+k0+k1*Δt.pk(n)

The coefficients k0 and k1 would be constantly modified by optimizingthe following equation for recent historical respiratory cycles againstT_(est):

T _(est) =t.Vmax(n)+k0+k1*Δt.pk(n)

Thus, the predictive trigger time T_(pred) may be determined by addingt_(T-PK) to the time of the most recent peak (PK) of the bio-Z signal,where:

t _(T-PK) =k0+k1*Δt.pk(n)

The predictive equation we are proposing is based on the fact that thevery most recent cycle times should be negatively weighted. Regressionanalysis supports this approach and indicates a negative weighting isappropriate for accurate prediction of onset. Thus, predicting onset ismore effective if the most recent historical cycle time is incorporatedinto an algorithm with a negative coefficient.

Description of External (Partially Implanted) System

With reference to FIGS. 51A and 51B, an example of an externalneurostimulator system inductively coupled to an internal/Implantedreceiver is shown schematically. The system includes internal/implantedcomponents comprising a receiver coil 910, a stimulator lead 60(including lead body 62, proximal connector and distal nerve electrode64). Any of the stimulation lead designs and external sensor designsdescribed in more detail herein may be employed in this genericallyillustrated system, with modifications to position, orientation,arrangement, integration, etc. made as dictated by the particularembodiment employed. The system also includes external componentscomprising a transmit coil 912 (inductively linked to receiver coil 910when in use), an external neurostimulator or external pulse generator920 (ENS or EPG), and one or more external respiratory sensors 916/918.

As illustrated, the receiver coil 910 is implanted in a subcutaneouspocket in the pectoral region and the stimulation lead body 62 istunneled subcutaneously along the platysma in the neck region. The nerveelectrode 64 is attached to the hypoglossal nerve in the submandibularregion.

The transmitter coil 912 may be held in close proximity to the receivercoil 910 by any suitable means such as an adhesive patch, a belt orstrap, or an article of clothing (e.g., shirt, vest, brazier, etc.)donned by the patient. For purposes of illustration, the transmittercoil 912 is shown carried by a t-shirt 915, which also serves to carrythe ENS 920 and respiratory sensor(s) 916, 918. The ENS 920 may bepositioned adjacent the waist or abdomen away from the ribs to avoiddiscomfort while sleeping. The respiratory sensor(s) 916, 918 may bepositioned as a function of the parameter being measured, and in thisembodiment, the sensors are positioned to measure abdominal andthoracic/chest expansion which are indicative of respiratory effort, asurrogate measure for respiration. The external components may beinterconnected by cables 914 carried by the shirt or by wireless means.The shirt may incorporate recloseable pockets for the externalcomponents and the components may be disconnected from the cables suchthat the reusable components may be removed from the garment which maybe disposed or washed.

The transmitting coil antenna 912 and the receiving coil antenna 910 maycomprise air core wire coils with matched wind diameters, number of wireturns and wire gauge. The wire coils may be disposed in a disc-shapedhermetic enclosure comprising a material that does not attenuate theinductive link, such as a polymeric or ceramic material. Thetransmitting coil 912 and the receiving coil 910 may be arranged in aco-axial and parallel fashion for coupling efficiency, but are shownside-by-side for sake of illustration only.

Because power is supplied to the internal components via an inductivelink, the internal components may be chronically implanted without theneed for replacement of an implanted battery, which would otherwiserequire re-operation. Examples of inductively powered implantablestimulators are described in U.S. Pat. No. 6,609,031 to Law et al., U.S.Pat. No. 4,612,934 to Borkan, and U.S. Pat. No. 3,893,463 to Williams,the entire disclosures of which are incorporated herein by reference.

With reference to FIGS. 51C-51G, alternative embodiments of an externalneurostimulator system inductively coupled to an internal/implantedreceiver are schematically shown. These embodiments are similar to theexternal embodiment described above, with a few exceptions. In theseembodiments, the receiver coil 910 is implanted in a positionedproximate the implanted stimulation lead body 62 and nerve electrode 64.The receiver coil 910 may be positioned in a subcutaneous pocket on theplatysma muscle under the mandible, with the lead body 62 tunneling ashort distance to the nerve electrode 64 attached to the hypoglossalnerve. Also in these embodiments, the respiratory sensor(s) 916/918 maybe integrated into the ENS 920 and attached to a conventionalrespiratory belt 922 to measure respiratory effort about the abdomenand/or chest. An external cable 914 connects the ENS 920 to thetransmitter coil 912.

In the embodiment of FIG. 51D, the transmitter coil 912 is carried by anadhesive patch 924 that may be placed on the skin adjacent the receivercoil 910 under the mandible. In the embodiment of FIG. 51E, thetransmitter coil 912 is carried by an under-chin strap 926 worn by thepatient to maintain the position of the transmitter coil 912 adjacentthe receiver coil 910 under the mandible. In the embodiment of FIG. 51F,the receiver coil 910 may be positioned in a subcutaneous pocket on theplatysma muscle in the neck, with the lead body 122 tunneling a slightlygreater distance. The transmitter coil 912 may be carried by a neckstrap 928 worn by the patient to maintain the position of thetransmitter coil 912 adjacent the receiver coil 910 in the neck.

With reference to FIGS. 51G-51K, additional alternative embodiments ofan external neurostimulator system inductively coupled to aninternal/implanted receiver are schematically shown. These embodimentsare similar to the external embodiment described above, with a fewexceptions. As above, the receiver coil 910 may be positioned in asubcutaneous pocket on the platysma muscle under the mandible, with thelead body 62 tunneling a short distance to the nerve electrode 64attached to the hypoglossal nerve. However, in these embodiments, theENS 920 (not shown) may be located remote from the patient such as onthe night stand or headboard adjacent the bed. The ENS 920 may beconnected via a cable 930 to a large transmitter coil 912 that isinductively coupled to the receiver coil 910. The respiratory sensor 916may comprise a conventional respiratory belt 922 sensor to measurerespiratory effort about the abdomen and/or chest, and sensor signalsmay be wirelessly transmitted to the remote ENS 920. As compared toother embodiments described above, the transmitter coil 912 is notcarried by the patient, but rather resides in a proximate carrier suchas a bed pillow, under a mattress, on a headboard, or in a neck pillow,for example. Because the transmitter coil 912 is not as proximate thereceiver coil as in the embodiments described above, the transmittercoil may be driven by a high powered oscillator capable of generatinglarge electromagnetic fields.

As shown in FIG. 51H, the transmitter coil 912 may be disposed in a bedpillow 934. As shown in FIG. 51I, the transmitter coil 912 may comprisea series of overlapping coils disposed in a bed pillow 934 that aresimultaneously driven or selectively driven to maximize energy transferefficiency as a function of changes in body position of the patientcorresponding to changes in position of the receiver coil 910. Thisoverlapping transmitter coil arrangement may also be applied to otherembodiments such as those described previously wherein the transmittercoil is carried by an article donned by the patient. In FIG. 51J, two ormore transmitter coils 912 are carried by orthogonal plates 936 arrangedas shown to create orthogonal electromagnetic fields, thereby increasingenergy transfer efficiency to compensate for movement of the patientcorresponding to changes in position of the receiver coil 910. FIG. 51Jalso illustrates a non-contact respiratory sensor 916 arrangement asutilized for detecting sudden infant death syndrome (SIDS). As shown inFIG. 51K, two orthogonal transmitter coils 912 are located on each sideof a neck pillow 938, which is particularly beneficial for bilateralstimulation wherein a receiver coil 910 may be located on either side ofthe neck.

With reference to FIG. 51L (front view) and 51M (rear view), externalrespiratory effort sensors 916/918 are schematically shown incorporatedinto a stretchable garment 945 donned by the patient. The sensors916/918 generally include one or more inductive transducers and anelectronics module 942. The inductive transducers may comprise one ormore shaped (e.g., zig-zag or sinusoidal) stranded wires to accommodatestretching and may be carried by (e.g., sewn into) the garment 945 toextend around the patient's abdomen and chest, for example. As thepatient breathes, the patient's chest and/or abdomen expands andcontracts, thus changing the cross-sectional area of the shape (i.e.,hoop) formed by the wire resulting in changes in inductance. Theelectronics module may include an oscillator (LC) circuit with theinductive transducer (L) comprising a part of the circuit. Changes infrequency of the oscillator correspond to changes in inductance of theshaped wires which correlate to respiratory effort. The electronicsmodule may be integrated with an ENS (not shown) or connected to an ENSvia a wired or wireless link for triggering stimulus as describedpreviously.

The garment 945 may include features to minimize movement artifact andaccommodate various body shapes. For example, the garment 945 may beform-fitting and may be sleeveless (e.g., vest) to reduce sensorartifacts due to arm movement. Further, the garment 945 may be tailoredto fit over the patient's hips with a bottom elastic band which helpspull the garment down and keep the sensors 916/918 in the properlocation.

Description of a Specific External (Partially Implanted) Embodiment

With reference to FIGS. 52A-52G a specific embodiment utilizing anexternal neurostimulator system inductively coupled to aninternal/implanted receiver is schematically shown. With initialreference to FIG. 52A, the illustrated hypoglossal nerve stimulatorincludes several major components, namely: an implantable electronicsunit that derives power from an external power source; a stimulationdelivery lead that is anchored to the nerve or adjacent to the nerve andprovides electrical connection between the electronics unit and thenerve, an external (non-implanted) power transmitting device that isinductively coupled with the implant to convey a powering signal andcontrol signals; a power source for the external device that is eithersmall and integrated into the body-worn coil and transmitter or is wiredto the transmitter and transmit induction coil and can be powered byprimary or secondary batteries or can be line powered; and a respiratorysensor such as those described previously.

These components may be configured to provide immediate or delayedactivation of respiration controlled stimulation. Initiation of thestimulation regimen may be by means of activation of an input switch.Visual confirmation can be by an LED that shows adequate signal couplingand that the system is operating and is or will be applying stimulation.As a means of controlling gentleness of stimulation onset and removal,either pulse width ramping of a constant amplitude stimulation signalcan be commanded or amplitude of a constant pulse width stimulationsignal or a combination thereof can be performed.

The electrical stimulation signal is delivered by the stimulation leadthat is connected to the implanted nerve stimulator and attached to orin proximity of a nerve. The implanted electronics unit receives powerthrough a magnetically coupled inductive link. The operating carrierfrequency may be high enough to ensure that several cycles (at least 10)of the carrier comprise the output pulse. The operating frequency may bein a band of frequencies approved by governmental agencies for use withmedical instruments operating at high transmitted radio frequency (RF)power (at least 100 milliwatts). For example, the operating frequencymay be 1.8 MHz, but 13.56 MHz is also a good candidate since it is inthe ISM (Industrial/Scientific/Medical) band. The non-implanted(external) transmitter device integrates respiration interface, waveformgeneration logic and transmit power driver to drive an induction coil.The power driver generates an oscillating signal that drives thetransmitter induction coil and is designed to directly drive a coil ofcoil reactance that is high enough or can be resonated in combinationwith a capacitor. Power can come from a high internal voltage that isused to directly drive the transmit induction coil or power can comefrom a low voltage source applied to a tap point on the induction coil.

With reference to FIGS. 52B-52E, the waveform generation logic may beused to modulate the carrier in such a way that narrow gaps in thecarrier correspond to narrow stimulation pulses. When stimulator pulsesare not needed, interruptions to the carrier are stopped but the carrieris maintained to ensure that power is immediately available within thestimulator upon demand. Presence or absence of electrical nervestimulation is based on respiration or surrogates thereof. Thetransmitted signal may comprise a carrier of about 1.8 MHz. To controlthe implanted electronics unit to generate individual nerve stimulationpulses, the carrier signal is interrupted. The duration of theinterruption is about equal to the duration of the output stimulationpulse. The stimulation pulses may be about 110 microseconds in durationand are repeated at a rate of approximately 33 per second. In addition,multiple pulses can be transmitted to logic within the implant tocontrol stimulation pulse amplitude, pulse width, polarity, frequencyand structure if needed. Further, onset and removal of stimulation canbe graded to manage patient discomfort from abruptness. Grading maycomprise pulse width control, signal amplitude control or a combinationthereof.

An indicator (not shown) may be used to show when the transmitter isproperly positioned over the implant. The indicator may be a part of thetransmitter or by way of communication with the transmitter, or a partof related patient viewable equipment. Determination of proper positionmay be accomplished by monitoring the transmitter power output loadingrelative to the unloaded power level. Alternatively, the implant receivesignal level transmitted back by a transmitter within the implant may bemonitored to determine proper positioning. Or, the implant receivesignal level that is communicated back to the transmitter by momentarilychanging the loading properties presented to the transmitter, such ashorting out the receive coil may be monitored to determine properpositioning. Such communication may be by means of modulation such aspulse presence, pulse width, pulse-to-pulse interval, multi-pulsecoding.

The transmitter may be powered by an internal primary power source thatis used until it is exhausted, a rechargeable power source or a powersource wired to a base unit. In the case of the wired base unit, powercan be supplied by any combination of battery or line power.

The respiration interface may transduce sensed respiratory activity toan on-off control signal for the transmitter. Onset of stimulation maybe approximately correlated slightly in advance of inspiration and laststhrough the end of inspiration, or onset may be based on anticipation ofthe next respiration cycle from the prior respiration cycle or cycles.The respiration sensor may comprise any one or combination of devicescapable of detecting inspiration. The following are examples: one ormore chest straps; an impedance sensor; an electromiographicalmeasurement of the muscles involved with respiration; a microphone thatis worn or is in proximity to the patients' face; a flow sensor, apressure sensor in combination with a mask to measure flow; and atemperature sensor to detect the difference between cool inspired airversus warmed expired air.

The circuit illustrated in FIG. 52F may be used for the implantedelectronics unit. There are five main subsystems within the design: areceive coil, a power rectifier, a signal rectifier, an output switchand an output regulator. The signal from the inductive link is receivedby L1 which is resonated in combination with C1 and is delivered to boththe power and signal rectifiers. Good coupling consistent with lowtransmitter coil chive occurs when the transmit coil diameter is equalto the receive coil diameter. When coil sizes are matched, couplingdegrades quickly when the coil separation is about one coil diameter. Alarge transmit coil diameter will reduce the criticality of small coilspacing and coil-to-coil coaxial alignment for maximum signal transferat the cost of requiring more input drive power.

The power rectifier may comprise a voltage doubler design to takemaximum advantage of lower signal levels when the transmit to receivecoil spacing is large. The voltage doubler operates with an input ACvoltage that swing negative (below ground potential) causes D1 toconduct and forces C2 to the maximum negative peak potential (minus adiode drop). As the input AC voltage swings away from maximum negative,the node of C2, D1, D2 moves from a diode drop below ground to a diodedrop above ground, forward biasing diode D2. Further upswing of theinput AC voltage causes charge accumulated on C2 to be transferredthrough D2 to C3 and to “pump up” the voltage on C3 on successive ACvoltage cycles. To limit the voltage developed across C3 so that anover-voltage condition will not cause damage, and Zener diode, D3 shuntsC3. Voltage limiting imposed by D3 also limits the output of the signalrectifier section. The power rectifier has a long time constant,compared to the signal rectifier section, of about 10 milliseconds.

The signal rectifier section may be similar in topology to the powerrectifier except that time constants are much shorter—on the order of 10microseconds—to respond with good fidelity to drop-outs in thetransmitted signal. There is an output load of 100K (R1) that imposes acontrolled discharge time constant Output of the signal rectifier isused to switch Q1, in the output switching section, on and off.

The output switching section compares the potential of C3 to that acrossC5 by means of the Q1, Q2 combination. When there is a gap in thetransmitted signal, the voltage across C5 falls very rapidly incomparison with C3. When the voltage difference between C5 and C3 isabout 1.4 volts, Q1 and Q2 turn on. Q1 and Q2 in combination form a highgain amplifier stage that provides for rapid output switching time. R3is intended to limit the drive current supplied to Q2, and R2 aids indischarging the base of Q2 to improve the turn-off time.

In the output regulator section, the available power rectifier voltageis usually limited by Zener diode D3. When the coil separation becomessuboptimal or too large the power rectifier output voltage will be comevariable as will the switched voltage available at the collector of Q2.For proper nerve stimulation, it may be necessary to regulate the(either) high or variable available voltage to an appropriate level. Anacceptable level is about 3 volts peak. A switched voltage is applied toZener diode D6 through emitter follower Q3 and bias resistor R5. Whenthe switched voltage rises to a level where D6 conducts and developsabout 0.6 volts across R4 and the base-emitter junction of Q4, Q4conducts. o Increased conduction of Q4 is used to remove bias from Q3through negative feedback. Since the level of conduction of Q4 is a verysensitive function of base to emitter voltage, Q4 provides substantialamplification of small variations in D6 current flow and therefore biasvoltage level. The overall result is to regulate the bias voltageapplied to Zener diode D6. Output is taken from the junction of theemitter of Q3 and D6 since that point is well regulated by thecombination of Zener diode breakdown voltage combined with theamplification provided by Q4. In addition to good voltage regulation athe junction of the emitter of Q3 and D6, the output is very tolerant ofload current demand since the conductivity of Q3 will be changed byshifts in the operating point of Q4. Due to amplification by Q3 and Q4,the circuit can drive a range of load resistances. Tolerable loadresistances above 1000 ohms and less than 200 ohms. The regulator hasthe advantage of delivering only the current needed to operate the loadwhile consuming only moderate bias current. Further, bias current isonly drawn during delivery of the stimulation pulse which drops to zerowhen no stimulation is delivered. As a comparison, a simple seriesresistance biased Zener diode requires enough excess current to delivera stimulation pulse and still maintain adequate Zener bias. As a furthercomparison, conventional integrated circuit regulators, such as threeterminal regulators are not designed to well regulate and respondquickly to short input pulses. Experiment shows that three-terminalregulators exhibit significant output overshoot and ramp-up time uponapplication of an input pulse. This can be addressed by applying aconstant bias to a regulator circuit or even moving the regulator beforethe output switching stage but this will be at the cost of constantcurrent drain and subsequently reduced range.

The implanted electronics unit may be used to manage the loss of controland power signals. With this design, more than enough stimulation poweris stored in C3 to supply multiple delivered stimulation pulses. Thisdesign is intended to ensure that the voltage drop is minimal on anyindividual pulse. One of the consequences is that when signal is lost,the circuit treats the condition as a commanded delivery of stimulationand will apply a single, extended duration, energy pulse until the fullstored capacity of C3 is empty. An alternative method may be to use anindirect control modulation to command delivery of a nerve stimulationpulse through logic and provide for a time-out that limits pulseduration.

To stimulate tissue, a modified output stage may be used to mitigateelectrode corrosion and establish balanced charging. The output stage isillustrated in FIG. 52G and includes a capacitive coupling between theground side of the stimulator, and tissue interface in addition to ashunt from the active electrode to circuit ground for re-zeroing theoutput coupling capacitor when an output pulse is not being activelydelivered.

Description of Alternative Screening Methods

Screening generally refers to selecting patients that will be responsiveto the therapy, namely neurostimulation of the upper airway dilatornerves and/or muscles such as the hypoglossal nerve that innervates thegenioglossus. Screening may be based on a number of different factorsincluding level of obstruction and critical collapse pressure (Pcrit) ofthe upper airway, for example. Because stimulation of the hypoglossalnerve affects the genioglossus (base of tongue) as well as othermuscles, OSA patients with obstruction at the level of the tongue baseand OSA patients with obstruction at the level of the palate and tonguebase (collectively patients with tongue base involvement) may beselected. Because stimulation of the hypoglossal nerve affects upperairway collapsibility, OSA patients with airways that have a lowcritical collapse pressure (e.g., Pcrit of less than about 5 cm water)may be selected. Pcrit may be measured using pressure transducers in theupper airway and measuring the pressure just prior to an apnea event(airway collapse). Alternatively, a surrogate for Pcrit such as CPAPpressure may be used. In this alternative, the lowest CPAP pressure atwhich apnea events are mitigated may correlate to Pcrit.

The critical collapse pressure (Pcrit) may be defined as the pressure atwhich the upper airway collapses and limits flow to a maximal level.Thus, Pcrit is a measure of airway collapsibility and depends on thestability of the walls defining the upper airway as well as thesurrounding pressure. Pcrit may be more accurately defined as thepressure inside the upper airway at the onset of flow limitation whenthe upper airway collapses. Pcrit may be expressed as:

Pcrit=Pin−Pout

where

Pin=pressure inside the upper airway at the moment of airway collapse;and

Pout=pressure outside the upper airway (e.g., atmospheric pressure).

Other screening methods and tools may be employed as well. For example,screening may be accomplished through acute testing of tongue protrudermuscle contraction using percutaneous fine wire electrodes inserted intothe genioglossus muscle, delivering stimulus and measuring one or moreof several variables including the amount of change in critical openingpressure, the amount of change in airway caliber, the displacement ofthe tongue base, and/or the retraction force of the tongue (as measuredwith a displacement and/or force gauge). For example, a device similarto a CPAP machine can be used to seal against the face (mask) andcontrol inlet pressure down to where the tongue and upper airwaycollapse and occlude during inspiration. This measurement can berepeated while the patient is receiving stimulation of the geneoglossusmuscle (or other muscles involved with the patency of the upper airway).Patients may be indicated for the stimulation therapy if the differencein critical pressure (stimulated vs. non-stimulated) is above athreshold level.

Similarly, a flexible optical scope may be used to observe the upperairway, having been inserted through the mask and nasal passage. Thedifference in upper airway caliber between stimulation andnon-stimulation may be used as an inclusion criterion for the therapy.The measurement may be taken with the inlet air pressure to the patientestablished at a pre-determined level below atmospheric pressure tobetter assess the effectiveness of the stimulation therapy.

Another screening technique involves assessing the protrusion force ofthe tongue upon anterior displacement or movement of the tongue with andwithout stimulation while the patient is supine and (possibly) sedatedor asleep. A minimum increase in protrusion force while understimulation may be a basis for patient selection.

For example, with reference to FIG. 53, a non-invasive oral appliance530 may be worn by the patient during a sleep study that can directlymeasure the protrusion force of the tongue as a basis for patientselection. The oral appliance 530 may include a displacement probe 532for measuring tongue movement protrusion force by deflection (D). Theoral appliance 530 may also include a force sensor 534 for measuring theforce (F) applied by protrusion of the tongue. The sensors in thedisplacement probe 532 and the force sensor 534 may be connected tomeasurement apparatus by wires 536.

FIG. 54 illustrates another example of a non-invasive oral appliance 540that may be worn by the patient during a sleep study to directly measurethe protrusion force of the tongue as a basis for patient selection. Theoral appliance 540 includes a displacement sensor 542 for measuringtongue movement and a force sensor for measuring tongue protrusionforce. The displacement sensor and the force sensor may be connected tomeasurement apparatus by wires 546.

Oral appliances 530 and 540 could be worn during a sleep study and wouldmeasure the tongue protrusion force during (and just prior to) an apneaevent when the protruder muscle tone is presumed to be inadequate tomaintain upper airway patency. The protrusion force measured as theapnea is resolved by the patient will increase as the patient changessleep state and the airway again becomes patent. The force differencemay be used as a basis for patient selection.

Another screening technique involves the use of an oral appliance withsub-lingual surface electrodes contacting the base of the tongue or finewire electrodes inserted into the genioglossus muscle to stimulate thetongue protruder muscle(s) synchronous with respiration during a sleepstudy. The oral appliance may be fitted with a drug delivery system(e.g., drug eluting coating, elastomeric pump, electronically controlledpump) for topical anesthesia to relieve the discomfort of theelectrodes.

For example, with reference to FIG. 55, an oral appliance 550 includes apair of small needle intramuscular electrodes 552 that extend into thegenioglossus. The electrodes 552 are carried by flexible wires 554 andmay be coupled to an external pulse generator (not shown) by wires 556.The electrodes 552 may be supported by a drug (e.g., anesthetic) elutingpolymeric member 558.

Alternatively, with reference to FIG. 56, an oral appliance 560 includesa cathode electrode 562 guarded by two anode electrodes 564 carried by asoft extension 565 that extends under the tongue. The surface electrodes562 and 564 contact the floor of the mouth under the tongue toindirectly stimulate the genioglossus. The electrodes 562 and 564 may becoupled to an external pulse generator (not shown) by wires 566. Theextension 565 may incorporate holes 568 through which a drug (e.g.,anesthetic) may be eluted.

Oral appliances 550 and 560 may be used during a sleep study andstimulation of the target tissue can be performed synchronous withrespiration and while inlet airflow pressure can be modulated. Theability to prevent apneas/hypopneas can be directly determined. Also thecritical opening pressure with and without stimulation can bedetermined. Alternatively or in addition, the intramuscular or surfaceelectrodes may be used to measure genioglossus EMG activity, either withor without stimulation. On any of theses bases, patient selection may bemade.

Patient selection may also be applied to the respiratory sensors todetermine if the respiratory sensors will adequately detect respirationfor triggering stimulation. For example, in the embodiment wherein bio-Zis used to detect respiration using an implanted lead 70, skin surfaceor shallow needle electrodes may be used prior to implantation todetermine if the signal will be adequate. This method may also be suedto determine the preferred position of the electrodes (i.e., optimalbio-Z vector). This may be done while the patient is sleeping (i.e.,during a sleep study) or while the patient is awake.

Description of Alternative Infra-Operative Tools

Intra-operatively, it may be desirable to determine the correct portionof the nerve to stimulate in order to activate the correct muscle(s) andimplant the nerve cuff electrode accordingly. Determining the correctposition may involve stimulating at different locations along the lengthor circumference of the nerve and observing the effect (e.g., tongueprotrusion). In addition or in the alternative, and particularly in thecase of field steering where multiple combinations of electrode contactsare possible, it may be desirable to determine optimal electrode orfiled shape combinations.

An example of an intra-operative stimulating tool 570 is shown in FIGS.57A and 57B. In this embodiment, the tool 570 includes a first shaft 571with a distal half-cuff 573. Tool 570 further includes a second shaft575 with a proximal movable collar 574 and a distal half-cuff 575.Stimulating tool 570 includes multiple electrodes 572 on half-cuff 573and/or half-cuff 575 that may be arranged in an array or matrix as shownin FIG. 57C, which is a view taken along line A-A in FIG. 57B. Thehalf-cuffs 573 and 575 may be longitudinally separated for placementabout a nerve and subsequently closed such that the half-cuffs 573 and575 gently grasp the nerve. The electrodes 575 may be sequenced througha series of electrode/field shape combinations to optimize (lower) thecritical opening pressure, airway caliber, tongue protrusion force orother acute indicia of therapeutic efficacy.

The tool 570 may be part of an intra-operative system including: (1)tool 570 or other tool with one or more stimulating electrodes that aredesigned to be easily handled by the surgeon during implant surgery; (2)an external pulse generator which triggers off of a respiration signal;(3) a feedback diagnostic device that can measure critical closingpressure intra-operatively; and (4) an algorithm (e.g., firmware orsoftware in the programmer) that is design to automatically or manuallysequence through a series of electrode configurations that will identifythe best placement of electrode cuffs on the nerves and configuration ofelectrode polarity and amplitude settings. Information from theintra-operative system may greatly speed the process of identifyingwhere to place the electrode cuff(s) on the hypoglossal nerve and whatfield steering may be optimal or necessary to provide efficacy.

Description of Miscellaneous Alternatives

The implanted neurostimulation system may be configured so thatstimulation of the nerve is set at a relatively low level (i.e., lowvoltage amplitude, narrow pulse width, lower frequency) so as tomaximize battery life of the INS and to minimize the chances that theelectrical stimulation will cause arousal from sleep. Ifapneas/hypopneas are detected, then the electrical stimulation can beincreased progressively until the apneas/hypopneas are no longerdetected, up to a maximum pre-set stimulation level. This auto titrationmay automatically be reset to the low level after the patient isawakened and sits up (position detector) or manually reset using thepatient controller. The stimulation level may be automatically reducedafter a period of time has elapsed with no (or few) apneas/hypopneasdetected.

The stimulation level (i.e., voltage amplitude, pulse width, frequency)may be adjusted based on changes in respiration rate. Respiration rateor patterns of rate change may be indicative of sleep state. A differentpower level based on sleep state may be used for minimal powerconsumption, minimal unwanted stimulation (sensory response), etc.,while providing adequate efficacy.

The electrical field shape used to stimulate the target nerve can bechanged while the system is proving therapy based on feedback indicatingthe presence (or lack) of apneas/hypopneas. The electrical field shapefor an implanted system can be changed by adjusting the polarity,amplitude and other stimulation intensity parameters for each of theelectrodes within the nerve stimulating cuff. An algorithm within theINS may change the currently operating electrical field shape if thepresence of apneas/hypopneas is detected, and then wait a set period oftime to determine if the new configuration was successful in mitigatingthe apneas/hypopneas before adjusting the field shape again.Additionally, the system may be designed to keep a log of the mostsuccessful stimulation patterns and when they were most likely to beeffective. This may allow the system to “learn” which settings to beused during what part of the night, for example, or with specificbreathing patterns or cardiac signal patterns or combinations thereof.

The proportion of stimulation intensity of two electrode cuffs used tostimulate a nerve can be modulated while the system is providing therapybased on feedback indicating the presence (or lack) of apneas/hypopneas.For example, one nerve stimulating electrode cuff may be place on themore proximal section of the hypoglossal nerve, while a second is placedmore distally. The proximal cuff will be more lady to stimulate branchesof the hypoglossal nerve going to muscles in the upper airway involvedwith tongue or hyoid retrusion while the more distal electrode cuff willmore likely stimulate only the muscles involved with tongue/hyoidprotrusion. Research suggests that to best maintain upper airwaypatency, stimulating both protrudes and retruders (in the rightproportion) may be more effective that stimulating protruders alone.Software within the INS may change the currently operating proportion ofelectrical stimulation going to the distal electrode cuff in proportionto that going to the proximal cuff based on the presence ofapneas/hypopneas detected. The system may then wait a set period of timeto determine if the new configuration was successful in mitigating theapneas/hypopneas before adjusting the system again. Additionally, thesystem software may be designed to keep a log of the most successfulstimulation proportion and when they were most likely to be effective.This may allow the system to “learn” which settings to be used duringwhat part of the night, for example, or with specific breathing patternsor cardiac signal patterns or combinations thereof.

The system described above may modulate electrical stimulation intensityproportion based on electromyogram (EMG) feedback from the muscles inthe upper airway being stimulated or others in the area. This feedbackmay be used to determine the correct proportion of stimulation betweenprotruders and retruders. The correct ratio of EMG activity betweenretruders and protruders may be determined during a sleep study for anindividual, may be determined to be a constant for a class of patientsor may be “learned” my the implanted system by using the detection ofapneas/hypopneas as feedback.

A library of electrical stimulation parameter settings can be programmedinto the INS. These settings listed in the library may be selected bythe patient manually using the patient programmer based on, for example:(1) direct patient perception of comfort during stimulation; (2) a logof the most successful settings compiled by the software in the INS(assumes apnea/hypopnea detection capability); (3) a sleep physician'sor technician's assessment of the most effective stimulation asdetermined during a sleep study; and/or (4) a list of the most effectiveparameters produced for a particular class of patient or other.

The electrical stimulation parameters described above may be adjustedbased on patient position as detected by a position sensor within theINS. The best setting for a given position may be determined by, forexample: (1) a log of the most successful settings compiled or learnedby the software in the INS (assumes apnea/hypopnea detectioncapability); (2) a sleep physician's or technician's assessment of themost effective stimulation as determined during a sleep study; and/or(3) a list of the most effective parameters produced for a particularclass of patient or other.

To avoid fatigue using a normal duty cycle or to extend the time thatthe upper airway is opened through neurostimulation, different parts ofthe genioglossus muscle and/or different muscles involved withestablishing patency of the upper airway can be alternately stimulated.For example, using two or more nerve or muscle electrode cuffs, the leftand right side genioglossus muscles can be alternately stimulated,cutting the effective duty cycle on each muscle in half. In addition,different protruder muscles on the ipsilateral side such as thegeniohyoid and the genioglossus muscle can be alternately stimulated tothe same effect. This may also be accomplished through one electrodecuff using field steering methods that selectively stimulated thefascicles of the hypoglossal nerve going to one group of pmtrudersalternating with stimulating the fascicles leading to a differentprotruder muscle group. This method may also be used to alternatelystimulate one group of muscle fibers within the genioglossus muscle withthe compliment of muscle fibers in the same muscle group.

To increase the ability of the upper airway to open during a (sensed)apnea/hypopnea through neurostimulation, different parts of thegenioglossus muscle and/or different muscles involved with establishingpatency of the upper airway can be simultaneously stimulated. Forexample, using two or more nerve or muscle electrode cuffs, the left andright side genioglossus muscles can be simultaneously stimulated,greatly increasing the protrusion forces. In addition, differentprotruder muscles on the ipsilateral side such as the geneohyoid and thegenioglossus muscle can be simultaneously stimulated to the same effect.This may also be accomplished through one electrode cuff using fieldsteering methods that selectively stimulated the fascicles of thehypoglossal nerve going to one group of protruders simultaneously withstimulating the fascicles leading to a different protruder muscle group.This may be achieved with one electrode cuff using field steering on amore proximal location on the hypoglossal nerve or two or more electrodecuffs, one on each branch going to a muscle involved with maintainingmuscle patency.

A sensor inside the INS (or elsewhere in system implanted) may detectbody position and automatically shut off stimulation when patient sitsup or stands up. This will prevent unwanted stimulation when patient isno longer sleeping. The device may automatically restart the stimulationafter the sensor indicates the patient is again horizontal, with orwithout a delay. The system may also be configured so that thestimulation can only be restarted using the patient controller, with, orwithout a delay.

The respiration signal using impedance and/or EMG/ENG are easily capableof determining heart rate. The stimulation may be interrupted or turnedoff when the heart rate falls outside out a pre-determined acceptablerange. This may be an effective safety measure that will decrease thechance that hypoglossal nerve stimulation will interfere with mitigatingphysiological processes or interventional emergent medical procedures.

Respiration waveforms indicating apneas/hypopneas or of other clinicalinterest may be recorded and automatically telemetered to a bed-sidereceiver unit or patient programmer. Respiration waveforms indicatingfrequent apneas/hypopneas, abnormal breathing patterns, irregular heartrate/rhythm may be recorded and automatically telemetered to a bed-sidedeceiver unit or patient programmer causing an alarm to be issued(audible/visible). The INS status such as low battery or systemmalfunction may also trigger an alarm.

Electrical stimulation intensity could be ramped up for each respirationcycle by increasing amplitude or pulse width from 0 to a set point toprevent sudden tongue protrusion or sudden airway opening causing thepatient to wake up. During inspiration, the system may deliverapproximately 30 pulses per second for a length of time of one to oneand one half seconds, totaling between about 30 and 45 pulses perrespiration cycle. Prior to delivery of these 30 to 45 pulses, amplitudeof each individual therapy pulse (in an added group of pulses) could beramped up from 0 to a set point at a rate of <10% of the amplitudeintended for the active duty cycle or 200 mS, whichever is less. Thepulse width of each individual therapy pulse could be ramped up from 0to a set point at a rate of <10% of the active duty cycle or 200 mS,whichever is less. Each of these ramp methods would require a predictivealgorithm that would stimulate based on the previous inspiration cycle.

Nerves innervating muscles that are involved with inspiration, such asthe hypoglossal nerve, have been shown to have greater electricalactivity during apnea or hypopnea. This signal cannot be easily measuredwhile simultaneously stimulating the same nerve. One method ofstimulating and sensing using the same lead is to interleave a sensingperiod within the stimulation pulse bursts during the duty cycle. Inother words, the sensing period may occur between pulses within thestimulation pulse train. This approach may be used with electrodes/leadsthat directly stimulate and alternately sense on a nerve involved withinspiration or on a muscle involved with inspiration or a combination ofthe two. The approach may allow sensing of apnea/hypopnea, as well astherapeutic stimulation.

From the foregoing, it will be apparent to those skilled in the art thatthe present invention provides, in exemplary non-limiting embodiments,devices and methods for nerve stimulation for OSA therapy. Further,those skilled in the art will recognize that the present invention maybe manifested in a variety of forms other than the specific embodimentsdescribed and contemplated herein. Accordingly, departures in form anddetail may be made without departing from the scope and spirit of thepresent invention as described in the appended claims.

1-74. (canceled)
 75. A method of treating an upper airway, the methodcomprising: delivering a first electrical stimulation to a first portionof a nerve innervating a first upper airway muscle via a plurality ofelectrodes adjacent the nerve; and delivering a second electricalstimulation to a second portion of the nerve innervating a second upperairway muscle via the plurality of electrodes, wherein the second muscleis different from the first muscle.
 76. The method of claim 75, whereinthe first electrical stimulation is delivered prior to andsimultaneously with the second electrical stimulation.
 77. The method ofclaim 75, wherein the first electrical stimulation is delivered for afirst predetermined time period, the second electrical stimulation isdelivered for a second predetermined time period, and the secondpredetermined time period is larger than the first predetermined timeperiod.
 78. The method of claim 75, wherein the first electricalstimulation differs from the second electrical stimulation in at leastone of amplitude and frequency.
 79. The method of claim 75, wherein thenerve is a hypoglossal nerve.
 80. The method of claim 79, wherein afirst electrode of the plurality of electrodes is positioned on thehypoglossal nerve at a location proximal of a portion innervating agenioglossus muscle and distal of a portion innervating a geniohyoidmuscle.
 81. The method of claim 79, wherein a first electrode of theplurality of electrodes is positioned on the hypoglossal nerve at alocation proximal of a portion innervating a geniohyoid muscle anddistal of portions innervating a hyoglossus muscle and a styloglossusmuscle.
 82. The method of claim 79, wherein a first electrode of theplurality of electrodes is positioned on the hypoglossal nerve at alocation proximal of portions innervating a genioglossus muscle and ageniohyoid muscle, and distal of portions innervating a hyoglossusmuscle and a styloglossus muscle.
 83. The method of claim 79, wherein afirst electrode of the plurality of electrodes is positioned on thehypoglossal nerve at a location proximal of portions innervating agenioglossus muscle, a hyoglossus muscle, and a styloglossus muscle. 84.The method of claim 75, wherein the plurality of electrodes includes atleast three electrodes, and delivering a first electrical stimulationincludes steering an electrical field to stimulate selected fascicles inthe nerve.
 85. A method of treating an upper airway of a patient, themethod comprising: positioning a plurality of electrodes adjacent anerve innervating a plurality of upper airway muscles; delivering afirst electrical stimulation to a first portion of the nerve innervatinga first muscle of the plurality of upper airway muscles; delivering asecond electrical stimulation to a second portion of the nerveinnervating a second muscle of the plurality of upper airway muscles,wherein the second muscle is different from the first muscle; andobserving the upper airway of the patient during delivery of the firstand second electrical stimulations with an imaging device.
 86. Themethod of claim 85, wherein the first electrical stimulation isdelivered prior to and simultaneously with the second electricalstimulation.
 87. The method of claim 85, wherein the first electricalstimulation is delivered for a first predetermined time period, thesecond electrical stimulation is delivered for a second predeterminedtime period, and the second predetermined time period is larger than thefirst predetermined time period.
 88. The method of claim 85, wherein thefirst electrical stimulation differs from the second electricalstimulation in at least one of amplitude and frequency.
 89. The methodof claim 85, wherein observing the upper airway of the patient includesvisually confirming an increase in a dimension of the upper airway. 90.A method of treating an upper airway of a patient, the methodcomprising: positioning a plurality of electrodes adjacent a nerveinnervating a plurality of upper airway muscles, the nerve including afirst set of fascicles innervating a first muscle of the plurality ofupper airway muscles and a second set of fascicles innervating a secondmuscle of the plurality of upper airway muscles, wherein the firstmuscle is different from the second muscle; selectively delivering afirst electrical stimulation to the first set of fascicles; andselectively delivering a second electrical stimulation to the second setof fascicles, wherein the first electrical stimulation and the secondelectrical stimulation are delivered repeatedly in an alternatingpattern.
 91. The method of claim 90, wherein the first muscle is agenioglossus muscle, and the second muscle is a geniohyoid muscle. 92.The method of claim 90, wherein the plurality of electrodes includes atleast three electrodes, and delivering the first electrical stimulationincludes steering an electrical field to stimulate selected fascicles ofthe nerve.
 93. The method of claim 90, wherein the first electricalstimulation differs from the second electrical stimulation in at leastone of amplitude and frequency.
 94. The method of claim 90, wherein themethod further comprises observing the upper airway of the patientduring delivery of the first and second electrical stimulations with animaging device.